Clinical Trial Drugs

Kill Cancer Stem Cells!

Cancer spreads and reoccurs because of  cancer stem cells.

According to the Mayo Clinic web site, stem cells are “the body’s master cells. All other cells arise from stem cells, including blood cells, nerve cells and others.”

Among the millions of cancer cells which form a cancer tumor, the stem cells are only 1-3% of them, but those stem cells are so resilient against chemo and radiation therapy and as long as even one stem cell survives  in our body, they can reproduce new stem cells and other cancer cells.

However, the scientists have been researching a drug to beat these deadly stem cells.  In 2006, Michigan University Cancer Center launched the first clinical trial in the world targeting breast cancer stem cells, and now the trial is in the phase lll.  This doesn’t sound far away to reach.

The drug is called MK-0752, which was originally developed for Alzheimer’s disease, and in the trial this drug is given to the patients with Docetaxel, a conventional chemo drug.

In the phase l and ll trials the stem cells were significantly reduced.  This is good news, but if even one stem cell can reproduce another stem cell or cancer cell, just reducing is not enough, I think.  However, I see various clinical trials using this stem cell targeted drug not only for breast cancer but also for ovarian, pancreatic, and children’s brain cancer.

Since I didn’t have good experience with Docetaxel, I wonder if MK-0752 can be given with T-DM1, which is more effective and has less side effects.

A Japanese pharmaceutical company, Dainippon Sumitomo Pharama, also has launched a phase lll clinical trial this year with a colon cancer stem cell targeted drug in the U.S. as well as in Canada.

Although there is  still a lot to be done to terminate cancer, the medicines are surely progressing and coming after cancer.  May God help scientists to get the victory soon!

The Island Where Cancer Vaccine Is Available

Grand Cayman Island is a British territory in Caribbean Sea. There, a cancer friend, who was diagnosed with stage 4 breast cancer, is trying to receive the most advanced cancer vaccine therapy, Dendritic Cell Vaccine.

Grand Cyman Island

I first learned about this vaccine from my brother-in-law in Japan.  After I shared this with the family of the cancer friend, the family found out that it was also available in Grand Cayman Island, where is much closer to the U.S. than Japan.

 “Order-Made” Therapy

A vaccine therapy is an “order-made” therapy to transform T-cells, one type of white blood cells, which takes the role of immune system and fights against pathogens or foreign objects, by taking out a sample of cancer tumor and teach them how to recognize cancer cells, so that they can go after cancer cells and destroy them.  There have been various vaccine studies but, Dendritic Cell vaccine (teaching dendritic cells, supportive cells for T-cells, how to recognize cancer cells) is the most successful so far according to a website.

The therapy includes only a surgery or biopsy to take out a cancer sample, and four injections during four months with the little side effect of fever that is the sign of  active immune system. The safety has been already proved by Phase l study.

 Why Cayman Island?

I thought the U.S. was the most medically advanced country where anything was possible.  Yet, this may not be true.  Because of the intense regulations of the FDA, there are treatments or medicines, which are approved in other countries but not in the U.S.

Perseus, the medical team picked the Cayman Island because the island is out of the FDA’s jurisdiction, but still close enough to bring patients from the U.S..

According to its site, Perseus followed all regulations of FDA and finished phase l & ll clinical trials for melanoma, and is in the process of approval of phase lll trial.  Yet, probably because the team is out of the FDA’s jurisdiction, it also  makes the vaccine available for other cancer patients, such with breast, colon, head and neck, lung, neuroblastoma, ovarian, prostate, and sarcoma cancer.

I pray my friend can make it to the vaccine!

Options May Increase By Doctor

“She is good.”

Satisfied with the new oncologist I left the hospital.

Actually I was her patient twice when the previous oncologist was on maternity leaves. I’ve sensed she was sharp during those times, and that’s why I requested her as my new doctor.

She gave me two options today:

One is NCI-Match/EAY131 clinical trial. Studying a patient’s cancer tumor, the researchers find out the best personal drug for the patient. This is a phase ll clinical trial.

The other one compares a new drug, Talazoparib or BMN673, which was designed for inherited breast cancer (all types), with a conventional drug, which a doctor chooses.

For NCI-Match study, a cancer tumor has to be at least 1.5cm. Since mine is still less than 1.5cm according to the last CT scan, this trial will be an option in the future.

For inherited breast cancer trial, since I don’t have anyone who had breast cancer in my family or relatives, It seems unlikely for me to have a genetic gene of breast cancer, and even if so, as the criteria of the trial limits only two regimen exposure for a candidate, I, who am on the 5th regimen don’t look eligible for the trial.

Anyway, I took both saliva and blood tests to find out if my cancer is genetic or not.

While the previous oncologist gave me only one choice from the next options, this new doctor wants to pursue every option including three from Dr. Slamon. (1. MM302 clinical trial 2. Affinitor + Herceptin 3. Halaven+ Herceptin) I feel like this difference is significant.

The doctor also ordered a bone scan because one of liver enzymes, ALP has been elevating since this summer and this could mean that cancer spread to the bones.

Listening to her, who made quick moves as if shooting many bullits, I thought I don’t need to be on guard all the time but relax trusting her.
It was an experience of learning that  options might increase by a doctor

Next Step

Herceptin is the must drug for HER2 positive breast cancer, which has otherwise a poor prognosis. Yet this promising drug doesn’t work for all the patients and even if it’s working, as the time goes by, it eventually loses the effectiveness. I have used Herceptin for 6 years continually, but cancer had grown even in the 1st & 2nd regimens until I added Tykerb. When I had two year remission, I was using Herceptin and Tykerb on top of other conventional chemo, and when I withdrew Tykerb, cancer became active again and has kept growing. Receiving the bad CT result, now I wonder if Herceptin is no more effective or maybe it wasn’t even from the very beginning.

In the email with the CT result, the oncologist asked me about a clinical trial with MM302, which was originally recommended by Dr. Slamon at UCLA. MM302 is a new drug of the same family with Adriamycin, which is one of major drugs for HER2 positive BC, but when the previous doctor wanted to use it for me in 2010, a genetic test (TOPO) indicated this drug was not compatible for me. So I have never used it yet. I emailed to the doctor who was in charge of this study asking if MM302 could be still beneficial for me or not. The reply came promptly but it said that the answer was unknown until I try it regardless of the status of TOPO test.
Since this study is about a sort of Adriamycin and Herceptin, which I started doubting the effectiveness, I am not sure if it’s worth betting.

I have googled other clinical trials for anti-resistant Herceptin. I found four, but practically only one was possible: It’s a study of Poziotinib, alternative of Herceptin, developed in China. In the phase I study this drug was effective for 60% of metastatic status women, who had failed with multiple regimens.

In the meeting with the oncologist, I discussed about MM302 and Poziotinib, and got agreement to explore the study of Poziotinib. Meanwhile I asked to add Tykerb, again, instead of Afinitor on current chemo, Abraxane and Herceptin. According to news, a recent study showed that Tykerb was much more effective than Herceptin at stopping breast cancer stem cells from growing when it was combined with the IL-8 drug.

Nobody knows if the 2nd round of Tykerb is effective on me or not until I try it. Chemo therapy is all big gambling, but this is what I will do next. I pray for God’s guidance continually.

Clinical Trial Requires Courage

Cancer treatment is always a gamble:  Yet clinical trials, especially the early stage ones appear even bigger gambles for me.

I have written about the TIL (Tumor Infiltrating Lymphocytes) treatment in this blog as one of the most exciting immunotherapies, and then recently I have read the update of the lady who has participated in this trial.  Judy, who had a recurrence three years ago with three year life expectancy after 10 year remission, was the first breast cancer patient in this trial while this treatment has been used successfully in Melanoma and Lymphoma.

According to the newspaper  article, first a surgeon removed one of her cancer tumors and sliced into 24 pieces.  Then in the lab, the scientists observed how her TIL would attack the cancer. The TIL attacked 4 sliced out of 24, but those active TIL were increased to 80 billion!

So far I was very excited, but the next paragraph in the article scared the life out of me:  Before she received those 80 billion active TIL, she had to “kill off” her own white blood cells, which didn’t recognize cancer cells, by a huge dose of chemo.

White blood cells protect our body from all kinds of infections.  They are the major part of the immune system. I have run a fever, had pneumonia, UTI, ect, all because my immune system was knocked down by chemo. So if she had to make “the tank empty”, I wonder what kind of reactions or side effects she had experienced and for how long.  No wonder this trial requires the participants to be admitted to an ICU.

She endured this process and was discharged at the beginning of this year.  Seems like she was in bed for a while even after the discharge, but after 5 months, her cancer is “melted away” and she is enjoying her normal life getting back to so many activities though her doctor said it is still too early to conclude if the trial was successful and the observation is necessary to continue.

I, who am intimidated already learning the details of my pick of Poziotinib trial, am such a coward compared with Judy.  We can have better treatments because the clinical trials move the studies forward, but without brave participants  like Judy, the trials are not possible.  Cancer battle requires lots of courage, and I am grateful and respect those trial participants, who are willing to take the big risks.

Clinical Trial Doc. Recommended

I tried a gene test to find out if there were any medicines which matched to my cancer, last year. Yet the oncologist said this gene matching trial is slight different from the last one using a different method and different investigated medicines.

In this phase 2 trial, there are 24 medicines, which effects and side-effects are studied in the trial. In the phase 1 trial, there were only 10 medicines, and maybe that was the major reason, but only 9% of the participants matched with those 10. This time in phase 2, the medicines were increased more than double and as new possible medicines are developed, those will be added in this trial. In this way, the scientists hope to boost up the matching rate to 20-25%.

This trial is not only for breast cancer patients but for patients who are running out of the treatment options or who are having difficulty finding the options, and have measurable cancer. Last Aug. when the trial began, so many applied that the trial was closed in just three months in Oct. The oncologist worries even this time, when the trial reopened, it may close quickly.

She is also concerned that Abraxane is not working anymore and adding Tykerb is not good enough. Yet, If I want to be in this trial, I have to hold the treatment for 10 weeks, and even after then, my chance to match the medicines is less than 20% or even 10%, and even if I match one of the investigated medicines, nobody knows if it will work or not.

Either way, staying on the current regimen or trying the clinical trial, my chance seems so little. I don’t know which is better. I have to pray for the guidance of God.

Vaccine Trial in Hitachi?

If the current regimen may not be effective enough and the clinical trial the oncologist recommended doesn’t sound exciting, either, I thought I should look for the 3rd option.
So I went back on the hunting. This time I used National Cancer Institute site instead of ClinicalTrials.gov.

When I used “Metastatic HER2 Positive Breast Cancer” as the key words, surprisingly 225 trials came up. There must be no other countries, which offered so many trials like the US, and I was so thankful that I lived in such an advanced country.

AS I looked through the 225 trials one by one, I found the dendritic cell vaccine trial I had written about in the blog two years ago. This is a phase 1 trial, which is the first time study with human beings, so there are so many unknown factors or risks, but as I scrolled down the page, I found it was available in CA, and under the line of “California”, I read Irvine- Hitachi Medical Systems America Inc.

Is it the same Hitachi, which produces appliances?
I checked the website of Hitachi Medical Systems America Inc. It looks like the company is selling medical imaging machines like a CT and MRI, but I couldn’t find anything about the vaccine or cancer study. A big question mark popped up in my head, but if this in not a mistake, Irvine is only an hour away from my house. This trial can be hopeful. I left a phone message at Hitachi and am waiting for the return phone call.

I Wish I Were A Mouse!

” In the mice study, the vaccine was successful.” I said.
Then a friend answered, ” I can make you a mouse bringing you a long tail, big front teeth, and cheese!”
Her joke made me laugh, but I really like her idea!

Though I haven’t heard anything from Hitachi yet despite two phone messages I left, I received some interesting additional information about the vaccine from NCI.

1) Cost

Expensive investigated drugs and all sorts of exams in the trial are sometimes covered by the study sponsors or sometimes to be subjects of individual health insurance. Since my insurance is Kaiser, which applies only for Kaiser hospitals, if a trial outside of Kaiser asks for a health insurance, it is almost impossible for me to participate the trial. Yet thankfully for this vaccine trial, NCI covers all the costs of the study including the traveling expense. This makes possible for me to fly to outside of CA if Irvine is not the option.

2) Procedure of Vaccine

Unlike ITL therapy, which requires to be admitted in an ICU, a patient’s white blood cells, which include Dendritic Cell (DC) are collected by 1-3 hour procedure using needles, which are shot under the skin. Once the vaccine is made by the collected DC, it is given four times. The side-effects appear to be flu symptoms like fever, fatigue, headache, etc, but only right after the vaccine injection, and other than that, it says the procedure of vaccine is safe and no need of hospitalization.

樹状細胞が含まれる白血球は、献血採血と似ていて、片腕から抜かれる血液は血液を分離する機械を通り、再び反対側の腕に戻される。

Collecting white blood cells for the vaccine is like a procedure of blood donation.  The circulated blood goes from the needle on one arm to a machine, which separate white blood cells from other blood cells and goes back to another arm.

3) Effectiveness

Since this is a phase 1 study, there is no data in human beings, but the theory is very impressive: While targeted drugs such as Herceptin, Perjeta, or Kadcyla, work only on the small part of HER2 protein, which characterizes HER2 positive cancer, the vaccine is supposed to induce antibodies to work much more comprehensively.

分子標的薬

Targeted drugs (Trastuzumab and Pertuzumab) recognize only a small portion of HER2 protein

The Vaccine is supposed to induce a patient’s immune system and make comprehensive antibodies called polyclonal antibodies.

左上よりワクチン接種後4日目、9日目、11日目、14日目、19日目、26日目

The shrinking cancer in the mouse

The problem is there is a huge gap between a mouse and a human being. It is not unusual that a clinical trial failed although the animal trial was successful.
Umm, I wish I were a mouse!

Minnie Mouse

Thinking More Of Vaccine Trial

Important role of vitamin D in Immune Functions

The Dendritic Cell vaccine trial checks vitamin D level by every four weeks. According to NCI (National Cancer Institute), “The exact role that Vitamin D deficiency plays in cancer has been controversial; but we do know that Vitamin D plays a critical role in cellular and immune functions within the body.” I know vitamin D and a baby aspirin could prevent cancer relapse, and actually I am taking vitamin D 4000IU/day, but it is interesting to see how vitamin D and the vaccine work together.

Clinical Trial is for future

Even though DC vaccine seems safe, this can fail with human beings. Since it is a trial, it requires frequent CT scans including not only the chest and abdomen but also bones and the brain. Exposure to huge doses of radiation is also scary, and I have to admit that the participants are human guinea pigs. Yet, I remember Mr. Aranami, the chairman of TRIO (Transplant Recipients International Organization) Japan as well as a good Christian, who passed away this spring with colon cancer, said he had chosen a clinical trial because he wanted to contribute to future patients. If I change the focus from myself to others, like Mr. Aranami did, probably nothing will be wasted and I’ll be able to accept becoming a “guinea pig”.

Need to Move Fast

The more I think of my options, the more I am leaning towards the DC vaccine trial. I am not sure if I am qualified for this trial, but the trial will accept only 65 participants in the nation and has already recruited 30 patients for part 1 study, which tested the safety of the vaccine and the dose of the vaccine. Then Part 2 will accept only 35. If I want to participate in this trial, I need to move fast. I emailed the oncologist about this trial with all the information I have received from NCI, and also called UCLA Medical Center to make an appointment with Dr. Slamon, who invented Herceptin, to hear his opinion about this trial. Most importantly, I am praying to open the door if this is God’s will.

“I Am Not Able To Refer You To The Trial”

The oncologist sent me a shocking reply this morning.
She can’t refer me because it is a phase one study.
I stared at the short paragraph email wondering if this was the answer from God.

It was yesterday that I was encouraged by a friend to be bold as I shared with her that I haven’t heard from NCI since last Tuesday though I sent the 2nd inquiry and maybe it was because the trial was closed recruiting enough participants. She told me to push by making a phone call to ask again.

Before I received the reply from the oncologist, I had emailed NCI again including two more contact persons this time. Reading the oncologist email, as I was wondering if I should let the trial go or not, the reply came from NCI. it answered my questions that 1) I, who has used multiple HER2 targeted drugs, can be qualified for the trial. 2) CT’s radiation doses are minimum, and 3) NCI is the only location that will make a personal vaccine. The trial is still open and so far I am qualified, which encouraged me to write back to the oncologist.

“The reasons why I am interested in the vaccine trial are:
1) the side-effects are mild and safe
2) I don’t need to hold the therapy for 10wk but only 2wk
3) If it works, the result will be greater than any other drugs according to the mice study
4) If it fails, I can go back to the conventional chemo quickly
5) I can try it right now when the brain is still clear (If cancer is in the brain, the patients are excluded from the study)

The reasons why I am concerned with the matching trial are:
1) While holding the therapy for 10-12wk, cancer may spread into the brain, and then I will be disqualified from most of the trials
2) my chance to match to the drugs seems very little.
3) Even if I match, the side-effects and the drug effects are unknown.”

She is a doctor and I am a patient. If there are any facts, risks, or concerns I don’t know, I will listen and humbly accept them, but I have to keep asking questions until I fully understand why she is right and agree with her.

A few hours later, the reply came. She said she would ask her group their opinions next week. I am thankful that she is open to consider my request.

I trust my Lord, who loves me and is with me, 100% whether the door of the vaccine opens or not. If this is His Will, the miracle will happen even in the very last minute just like the Hawaii trip. I pray and wait upon His answer patiently again.

Decision

I made a decision to apply for the Denderitic Vaccine Trial.

Yesterday I requested Kaiser to prepare all information needed for the trial, but the trial will close any day once the participant number reaches 30. If my information arrives over there on time, the institute will evaluate it to determine my eligibility, and if I am eligible, I will be invited to the institute hospital for a physical exams including CT scans and lab tests. It is a long way to go to be accepted.

Two days ago, when I saw the oncologist, she said that she didn’t think the vaccine was ready yet, and the matching trial would give me better chance to control cancer just as she explained in the email. I also repeated the same as the reply saying the reasons why I was leaning towards the vaccine trial.

Her denial of the effect of the vaccine affected me, but still, I was not convinced that the matching trial was a better choice.

She said three-months-off therapy would be safe because my cancer has been progressing slow, but what if she is wrong? And what if I would not match with any drugs after then? Even if I found a drug, how much effect could I expect from only single drug? Or the side effects could be so severe that I might not be able to continue the drug. If I thought of the price as it fails, her explanation was not good enough to change my mind and I know that even if I accept her choice, without the success, I would deeply regret and blame her.

” If you still want to try the vaccine, you have to pay from your pocket,” said she.
Oh, when she said no referral, she meant the insurance!
As I told her the institute would pay all the cost of the trial including for traveling, she said, “Then I don’t need to bring it to the meeting. Go and do it.”

Regarding the cost was on the letter I had attached to the email to her. Not knowing even the location of the trial, she didn’t seem to have read the attached. Maybe she didn’t need to know any of such but the fact that this is the phase 1 dendritic vaccine trial, which was enough for her to conclude, and she might think I was a stubborn foolish patient though, at the end of the meeting, she accepted my choice, or she had to accept it.

Going against the doctor’s opinion made me depressed. As I got home, I read the long letter of the information regarding the vaccine trial once again. If I have to choose a clinical trial, even if the vaccine trial is phase 1, the benefit as it works, and the risks as it fails look still better than the matching trial. I drew the same conclusion.

” God, if I am heading to the wrong direction, please close the door and stop me.” Praying so, I’m also hopeful remembering the prayer of healing in Bethesda in Israel where I traveled two years ago, the same name city as where the trial is held in MD.

National Cancer Institute (NCI)

I am not sure if I can participate in the vaccine clinical trial or not yet and I should prepare the next option though, the more I learn about NCI and the city Bethesda in MD, the more I anticipate. If I set my expectation high and it won’t go my way, I will be very disappointed, but it is getting harder to control my expectation.

The city’s name Bethesda, which means House of Mercy in Aramaic, came from a local small church, and the church took the name from the pool Bethesda in Israel, where Jesus performed a miracle of healing on a disabled man, who was waiting for 36 years to get into the pool, which had a healing power when the water was stirred. So many sick and disabled people were waiting to get into the water that he didn’t had a chance to get in. Yet Jesus healed him by commanding him to rise and walk (John 5:2-18). Two years ago at the pool Bethesda in Israel I visited, I prayed for the cure from cancer.

In Bethesda in MD, which is only 13km north from Washington D.C, there are several huge national medical organizations and it appears like a city of medicine. I didn’t know until now, but NCI is a part of National Institute of Health, which is the oldest and the primary medical organization in the U.S. “with 1,200 principal investigators and more than 4,000 postdoctoral fellows” according to Wikipedia. Compared with this place, not only Kaiser, but even UCLA Medical Center looks so tiny.

I really long to visit Bethesda, MD as well as this giant health organization! Since I had to send the all the information for the trial by myself, I am worried if they have arrived at the right place on time, but, I hope they had and to hear that I would have passed the first screening, the first step to go to Bethesda.

The 2nd Opinion from Dr. Slamon

I was worried if the information for the vaccine trial I sent to NCI had been arrived at the right place or not, but thankfully it did. Monday NCI sent me a lot of consent forms and I sent back with signature next day. I will hear about next step in next week.

Meanwhile, I visited Dr. Slamon, who had invented Herceptin, at UCLA yesterday. Usually I have to wait for a few months to see him, but this time it was quick.

First I asked him about Afinitib, one of 24 drugs in the MATCH clinical trial, the primary oncologist recommended . In this trial, patients take a gene test to find some matching drugs out of the 24 drugs regardless of the location or the type of cancer. I may find more than one drug, but it looks like there are only two available for HER2 positive, my type. One is TDM1, which I’d already used two rounds, and another is Afinitib, an investigated new drug.

Dr. Slamon said that this drug was expected to work like the combination of Herceptin and Tykerb, which I have used since 2011 and already have allowed progression. So he didn’t recommend this trial.

Second, he answered me about Immune Checkpoint Inhibitor clinical trial, which I learned from a Japanese cancer patient in Germany, who had sent me a comment on my blog. He said this trial is open at Cedars Sinai Hospital, which is as big as UCLA in LA, and gave me the investigating doctor’s name and her phone number. This is his first recommendation for me. I called there this morning and requested the written information.

Third, he said OK with the vaccine trial though it would take a long time to see the effect. I asked how long, and then he said a few months.
“Meanwhile will cancer grow?” I asked again. He said NCI would explain for that answer but it may be stable.
The vaccine will be given every four weeks for the first three injections and lastly in 8 weeks. It will take about 5 months to complete, so he might mean until the completion of the vaccine, the effect won’t be seen. Because cancer is a progressing disease, if it’s stable, this is also good effect I believe. Yet in the mice study the cancer grew before it started shrinking. If cancer grows in five months while I finish 5 injections of the vaccine, that would be scary.

Lastly if I won’t participate in a clinical trial, I have only two unused drugs left. I asked if I could use them with duo of Tykerb and Herceptin because I feel like Herceptin is no more effective. He said, ”Yes.” “With the same dosage as of now.”

It was a good meeting with good feedback. As I will see my primary oncologist tomorrow, I’m going to bring those 2nd opinions and review the next strategy with her, but until it becomes clear if the checkpoint trial is surely my option, I will continue to pursue the vaccine trial.

It has been a year since the last visit to Dr. Slamon though, I could discuss more new therapies. If I can buy time, someday I may be able to see the day to beat cancer.

Immune Checkpoint Inhibitor Drug Trial

It took a week to receive a reply from Cedars. After I requested again the information of the immune checkpoint inhibitor trial, the email I receive said that there was no such a trial.
Since I heard of the Immune checkpoint inhibitor drug, I have been searching the trial, and because the trial for HER2 positive breast cancer was only available in Europe and I couldn’t find anything but for triple negative breast cancer in the U.S., I almost accepted the reply.

Yet as I forwarded this reply to Dr. Salmon’s office, his nurse recommended asking Cedars once again, so I did. This time Cedars said there was the trial. Yet, I couldn’t identify any key words such as “checkpoint”, “PD1”, or the drug name “Keytruda” in the description of the trial I was given. It looks like a totally different trial. So I am asking UCLA again to confirm if this is the right trial I am looking for.

Meanwhile I learned that the inhibitor drug, Keytruda, was already approved for melanoma and non-small cell lung cancer in the US. If PD1 expression, a biomarker of cancer, is high, Keytruda appears very effective.
Yet the side effects could be serious causing pneumonitis, holes in the intestine,etc, and in the worst case, the stimulated immune system may attack the healthy organs and tissues, which leads to death.
A Japanese lady, who has been on this drug in Germany, said her cervical cancer has shrunk dramatically with little side effects. Her case must be very successful, but I, who have seen a liver transplant patient, who had died because his immune system attacked himself, was intimidated and feel like I don’t mind if this trial is not available yet.
Every choice seems very risky with a slim chance. I have to trust the Lord and pray to lead me to the right therapy!

“What Happened with Clinical Trial?”

People have asked me the clinical trials’ status, but it is difficult to explain.

First I sent the consent forms for the vaccine trial about two weeks ago, and am waiting for the next cue.

Second, after some confusion, finally I got the right name of the immune checkpoint inhibitor trial from Cedars Sinai. However, When I looked at the description of the trial, the investigated drugs in the trial,Ibrutinib & MEDI4736 are different from The drug, Keytruda, which I learned from Mrs. E in Germany.

Ibrutinib is a cancer targeted drug, which is already approved for blood cancer like Leukemia by FDA, and MEDI4736 is an investigated PD1 inhibitor drug, which has been studied for non small lung cancer, but it seems like that both are the first time to study with breast cancer.
The side-effects of MEDI4736 seems mild, but Ibrutinib may cause bleeding, plunging platelet count, infection, and even different cancer! Though the trial sounds so scary, Mrs. E, who has been on Keytruda, said the drug gave her back the normal life with almost zero side effects.

A PD1 inhibitor drug works when PD1 expression is high. If my PD1 expression is low, this trial won’t be an option anyway, so I am asking different sources how to check the PD1 expression.

Meanwhile my primary oncologist mentioned about a phase 2 cancer targeted drug clinical study. This investigated drug is designed to respond to certain cancer genes. I asked her to send me the details of this trial.

It must be good to have more than one option, but so far every option seems to have high risk, and I don’t know which one is the best. I have to keep praying for God’s guidance.

Vaccine Responded 50%

“A vaccine therapy has not been successful.”

From my oncologist, the NY Times article, and more different sites, I have heard or read the same message. Dr. Slamon at UCLA didn’t oppose this option, but told me that it may take a long time to see the response.

Uncertainty makes me nervous, and difficult to choose the right trial, yet the vaccine trial has had phase 1 part 1 study inviting 30 participants already. I decided to ask questions directly to the investigating doctor of the vaccine study in order to solve uncertainty.

The reply came right away. Using a war analogy the doctor explained that conventional chemo or radiation therapy is like dropping a bomb, but the vaccine is like training special soldiers how to find and fight the enemy. So the vaccine takes longer than chemo or radiation to respond.

Then she gave me the data:
Out of 10 participants, who received intermediate and high dosages of the vaccine, 5 had clinical responses, which means 50%. Out of 5, one had a complete response, which means cancer was gone 100%. Another one had a partial response with 72% reduction of the tumors, and the other three were stable. Those participants are not breast cancer patients but all of them have HER2 positive cancer. HER2 positive breast cancer participants have been recluted in the study since Mar. in this year, and so far there are only 5 participants. Their data is still immature but three are stable and the other two’s cancer has grown, which was expected based on the mice study, but the densities are getting lighter that can be the sign of cancer dying from the inside of tumors.

Usually if the response rate is 20%, the scientists consider it good, so 50% sounds really good to me, and although it is the early stage, the response rate of breast cancer participants looks like 100%.

CT scans are taken every 8 weeks to observe the response though, the earliest response was observed in the 8th week, and more were observed in the 16th week. This is also helpful.

It was no way possible to gain such fresh information 10 years ago. Now because of Internet it is possible. Being deeply thankful for the doctor who answered throughly and quickly, I forwarded the reply to the primary oncologist.

Changing The Plan

Sometimes when we have a strong feeling, we think God is guiding or talking to us.  Yet, the feeling doesn’t  always go with His Will and if we believe the feeling should guide us, we may make a wrong choice.

I am talking about myself.  My feeling was ( or even “is”) voting for the vaccine trial, but I decided to choose a cancer targeted drug, Entrectinib trial the primary oncologist recommended, as the first, and the vaccine as the second.  The immune checkpoint inhibitor drug trial, I asked about at UCLA, will be the third.

After the NY Times published articles about the checkpoint inhibitor drugs, I saw people started talking about the drugs here and there.  I didn’t know, but former president Carter has shrunken his brain cancer with this inhibitor drug,  Keytruda.  This must be really promising, but the available trial of this kind for me is the phase 1 using different drugs, which made me afraid of the side effects such as autoimmune disorder or different cancer.  So this choice will be for the future.

On the other hand, the targeted drug trial is phase 2, and in phase 1 of this study, the response rate was 75%, which is better than 50% of the vaccine response rate.  In this trial, first I have to have the cancer tissue test, which takes two-three weeks. If there is no match between the DNA and the drug, this trial is not for me and I want to try the vaccine, but even just to have the tissue test, I was told to withdraw the consent forms from the vaccine trial.

This morning, I actually received the confirmation email of my eligibility for the 2nd screening for the vaccine.  It took about a month to get this confirmation, and I was about ready to have the 2nd screening such as CTs and blood tests.  If I am not qualified for the targeted drug and want to pursue the vaccine again, do I have to start all over again?  I am asking about it to NCI.

If I am eligible for the targeted drug, Entrectinib, I have to take the drug as long as it works, but with the vaccine I may be able to put the final period of the cancer battle just after four shots.  Such ideas stir up my feeling, yet I should not let the feeling control over the decision.  75% is better than 50%.  Phase 2 is better than phase 1.  My oncologist recommended it.  I don’t have to travel to Maryland.

Anyway, I am learning that it’s a long process to just get in a clinical trial.  I can be patient because I am on the chemo therapy.  Yet if I were off chemo or knowing cancer is growing, no way I can handle this.  Probably this is another Grace of God.

Progress

Being stuck in between two clinical trial’s systems, I was getting weary.
A week ago I emailed NCI asking if the vaccine study team could keep my information in case I want to pursue the vaccine again – though currently I have to withdraw.

Because there hadn’t been any reply, I also emailed the Kaiser research director asking if holding the consents for the vaccine instead of withdrawing would be acceptable for the gene test. That was last Friday.
This week, a clinical research nurse called and emailed me saying she would like to help me. I thought great, but after exchanging numerous emails and phone calls, I was referred to the same nurse, who first told me to withdraw from the vaccine trial., to confirm if I don’t have to withdraw! For three days I worked hard but I was making a circle and coming back to the starting point. It was discouraging and disappointing.

Big sigh ;-(

Then I started over; emailing to the director,” May I ask you the same question once again?’

A Story of Sara

Being weary, I remembered about Sarah, Abraham’s wife, in Genesis. She, who could not wait for the fulfilment of God’s prophecy that she would give a birth to a son, gave her slave Hagar to Abraham to have a child (Ishmael). Yet, eventually Sara became pregnant and indeed gave birth to Isaac. The tension and hostility grew in-between two mothers as well as two sons, and has continually grown between the offsprings of Ishmael, Muslims, and the offsprings of Isaac, Jews and Christians, even creating terrorists ISIS in this century. Because she was inpatient and acted on her own, the consequence was horrible. Maybe why I am in the maize without progress is that I am acting like Sarah instead of waiting for God opening the door…

Breakthrough

As I was writing so far, I noticed there was an email from Kaiser. I opened it….Yes! The answer was given!
The Kaiser doctor, who is in charge of the study accepted my request and allowed me to hold the consents for the vaccine. NCI will keep my medical information and my place in line so that I can go back to the vaccine trial if I am not qualified for the targeted drug trial at Kaiser.
Now I can turn in the consent forms for the gene test!

In the email from the Kaiser research director, she said,
“Your persistence paid off. So good for your Kathy, you keep on fighting. We all wish you well.”

Thank you Jesus! GOD IS GOOD ALL THE TIME!

Still In the Waters of Clinical Trial System

I thought I would be in the trial by now when I first decided to apply for a clinical trial in June. The reality is I am still waiting to be accepted for a trial. My summer was just researching and swimming in the waters of complicated clinical trial systems.

Last week when I was finally able to avoid withdrawing the consent from the vaccine trial, I thought now I was moving forward turning in another consent form to the gene test for the targeted drug. Yet this week I was told that the consent forms I turned in were invalid because I had to sign in front of a clinical nurse! Another big sigh.

Today finally my consent forms were accepted. I’m not sure when my cancer tissue will be sent to the lab for the gene test, but it will take about three weeks to get the result. If there is not enough tissue, I have to have a biopsy to collect the cancer tissue, so it will take longer. Then if the gene test result allows me to take the trial drug, I will take CT scans and labs as the physical screening, and then I have to hold off from chemo for four weeks to start the drug. So it will take at least two more months to be on the drug.

Then there was one more surprise waiting for me. When I asked how many people have been in the trial so far, the oncologist said, ” 200 people took the test and 5 were eligible. It’s like winning a lottery.”

5 out of 200!
I am so glad that I didn’t withdraw from the vaccine trial. In order to make a decision of a trial, I learned what I should ask for the first place. Actually I am wondering if I should go back to the vaccine trial now without waiting for the result to save the time. Readers, what do you think? I have to pray.

I Quit

I decided to quit the Ignyta trial, the targeted drug trial.  Since yesterday when I heard that the matching rate of the gene test was less than 3% (5 out of 200), I have prayed and pondered if I should stay on the course or change to the vaccine.  The reason why I chose the targeted drug over the vaccine was because I had read that the drug’s response rate was 75% once it matched.  Yet I didn’t know the matching rate was so little.

The only condition to try the gene test seems if the current regimen is working.  Yet unless I take a CT, which I don’t want, or maybe an x-ray, I’m not able to know it. If I go back to the vaccine trial, the next step is a physical screening (CTs and lab tests), but I don’t know how long I have to wait for that.  Do I want to waste three weeks in such a case?  No.  That is my conclusion.

I emailed my oncologist and the clinical study nurse to let them know that I want to cancel the consents.  I was going to email NCI to go back to the vaccine trial, but I thought I should wait for the oncologist’s reply just in case – to make sure if I am misunderstanding what she said yesterday.

Nothing is certain  and everything is a gamble.  Regardless of my choice, I may be facing the dead end.  Or, regardless of my choice, God can sustain my life if that is His Will.