I met with MO's at Penn and Jefferson last week to review options for responding to active cancerous growth. They both mentioned 4 options but each ruled out 1 quickly. I had appointments with each last week. Penn on Monday and Jefferson on Tuesday.
The following are the options given to me.
1. Switch from Zytiga to another hormonal medication like Xtandi. Ruled out. Both Doctors say results have not supported this as an effective treatment for metastatic castration-resistant disease.
2. Chemotherapy-likely Docetaxel.
3. Radium 223 to treat the disease in my bones appears to be the only problem areas. No evidence of lymph nodes, soft tissue, or organs being involved.
4. Immunotherapy--both institutions have multiple phase 2 and phase 1 trials going.
Immunotherapy is a direction I am very interested in. After the meetings, both Doctors indicated that it would take a while, perhaps months, to get into an immunotherapy program. I decided to keep both doors open, though I am more comfortable at Penn, and I had one foot out the door.
Since I need to slow the growth of cancer, the likely choice that I would be making a is between chemo or radium 223. This story has so many moving parts that I am getting confused keeping this note in the proper tense. I decided to try to get Chemo started quickly, but that may be a moot point, as described below.
There is no evidence of cancerous growth anywhere but in my bones, but after talking it over with the two MO's and the RO at Penn, I decided that chemo would work on the disease even if it is not showing up on scans yet.
In the meantime, the Penn doctor ordered a Guardant 360 genetic analysis. The Guardant technician met me at my son’s house on Saturday where I was helping him move in. That is very responsive and great service from Guardant which is a California company. I should have a DNA and RNA analysis in about a week.
Much to my surprise, the Jefferson MO called me on Saturday to say that a spot had opened up in one of the programs there. WOW. He sent a note today describing the program with an opening that will be able to accept me quickly if I qualify.
Here is his description of the program I might get into: "REGN5678 is a PSMAxCD28 human IgG4-based bispecific antibody (bsAb) being developed in combination with the anti-programmed death-1 (PD-1) monoclonal antibody (mAb), cemiplimab (REGN2810), for the treatment of prostate cancer. REGN5678 is designed to target prostate tumors by bridging prostate-specific membrane antigen (PSMA)+ tumor cells with CD28+ T cells and providing amplified T cell receptor (TCR)-CD3 complex-mediated T cell activation within the tumor through the activation of CD28 signaling. Currently we are recruiting to the phase 1, first-in-human study of REGN5678 in patients with relapsed/refractory metastatic castration-resistant prostate cancer (mCRPC) that have good performance status and have progressed on standard treatment options. "
If I get into this program promptly, my understanding is that I won’t be doing the chemotherapy. I could be wrong about this as I took the call about the opening while in the car.
I am pushing both institutions, and they are both responding. I am on a roller coaster of processing information and trying to keep my emotions under control.
There are so many thoughts and questions in my head now. I will ask one to the group for now. Is going right to the immunotherapy program and skipping chemotherapy too risky? It seems like chemo is a known quantity while immunotherapy is just developing.
It fits my personality to go for immunotherapy.
I apologize for this stream of consciousness that has a convoluted progression of thoughts and events that are not in the order that they happened.
I have left out other peaks and valleys of the week to try and focus on the choices at hand as it developed with the Saturday call.
I look forward to hearing your thoughts.
Thanks
Philly
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Philly13
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My opinion is to stay with the effective, proven treatments if they are available, especially when the alternatives are Phase 1 or Phase 2 clinical trials.
I agree that switching anti-androgens is not likley to work for long if it works at all.
If I were in this situation, I would first wait to to see if there are any treatable mutations. For example, if I came back with a BRCA2 mutation, I would try a PARP inhibitor first. If there aren't any, Docetaxel chemotherapy would be my first choice. I've had it already so I know that it's tolerable for me.
That's just my opinion. Wishing you the best in your decisions.
I think the BiTE trials look very good now that they have gotten the dosing correct. UPenn also has the PSMA CAR-T trial. My understanding is that it is only a few infusions, and then you can move onto chemo.Is that not the case?
MSK has recently opened its Th-227-PSMA trial, which looks particularly good for men with predominant bone metastases. Check out the list of trials at the end of this article:
“AMG 509 is a bispecific XmAb® 2+1 immune therapy designed to redirect T-effector cells to kill STEAP1-expressing cells. AMG 509 contains two identical humanized anti-STEAP1 Fab domains that bind STEAP1-expressing cells, an anti-CD3 single-chain variable fragment (scFv) domain that binds T cells, and an effectorless Fc domain that extends serum half-life. Currently we are recruiting to the phase 1, first-in-human study of AMG 509 (single agent) in patients with relapsed/refractory metastatic castration-resistant prostate cancer (mCRPC) that have good performance status and have progressed on standard treatment options.”
“The CART-PSMA-TGFβRDN-02 (Study CART-PSMA-02) study is an open-label, multi-center Phase 1 study to assess the safety, tolerability, feasibility and preliminary efficacy of the administration of genetically modified autologous T cells engineered to express a CAR capable of recognizing the tumor antigen PSMA and a dominant negative TGFβ receptor. This study is a Phase 1 study that aims to explore doses and schedules of the CART-PSMA-TGFβRDN cells in patients with relapsed/refractory metastatic castration-resistant prostate cancer (mCRPC) that have good performance status and have progressed on standard treatment options. For this trial, patients will need to have their tumor evaluated for PSMA expression. “
I believe the CART-PSMA test is at UPenn and Jeff. I am reaching out to MSK and Cornell-Weill.
I am collecting info and will report to the group,as more data is collected.
I believe the REGN 5678 is increasing dosage through the series.
During these 18 years, I have been in clinical trials and I got some benefits, so I am biased in favor of the trials. I would consider the trial you have been offered (you need to find out about side effects which could be intense in some of these immunological trials). I will also consider the trial mentioned by TA about Th 227 PSMA at the MSK .
If you get into a trial and you have side effects that you can not tolerate or there is progression of the cancer, you can drop immediately from the trial and start chemo. IMO it is a no-brainer.
Hi Tango, I’m starting to explore clinical trials so that I have an option after I finish with Xofigo which I start next week. How many trials have you tried?Do you mind if I ask which ones you have done and which ones were most beneficial? Does it take a lot of time to get enrolled in one? How did you pick the trials that you participated in? Sorry about all of the questions but I know almost nothing about them.
It does take time to get enrolled in a trial. One needs to gather all the medical information they request. It will help if you start soon to get all the visits, notes, tests, radiological studies (CDs and reports) , pathological reports, slides etc. You can request them for continuation of care. Most institutions will not charge you for sending this information.
I select clinical trials I know I will get a test or a treatment, basically not randomized placebo trials.
I entered a vaccine trial in 2007. I had a PSADT of less than 3 months at that time. I received the vaccine from January 2007 to February 2009. My PSA stop increasing (no other treatment) and remained stable until 2013. Then started to increase with a PSADT of more than 15 months. Eventually accelerated. In 2016 my PSA was 2, no metastases and I was admited to a new vaccine trial with the same vaccine, but this time it did not work and caused a peripheral neuropathy. I dropped immediately from the trial, 10 months before completion..
My PSA continued to increase, no metastases in bone or CT scans and I decided to enter a clinical trial for Ga 68 PSMA PET/CT which detected metastases in lymph nodes. Using this test I applied for a trial of Lu 177 PSMA in Germany in 2016. One treatment caused all the mets to become PSMA negative.
Look for immunological trials, nuclear medicine trials with Lu 177 PSMA, Ac 225 PSMA, Thorium PSMA or similar, new anti androgens, new forms of chemo etc. You can search in clinicaltrials.gov.
You can request help from your doctors, but in my experience they recommend trials being done by them or their institution. You should try to get a second and a third opinion about your clinical situation, if it is possible financially. Good places to consult are the MSK in New York, the Dana Farber in Boston , the MD Anderson in Houston, the Cleveland Clinic, UCSF, UCLA etc. These consults can put you in touch with several clinical trials.
Tango, thanks so much for our guidance. For the lu-177 trial In Germany, how did you find that one? Is there a resource somewhere for trialS taking place in Germany?
I contacted the institutions directly. I searched for medical articles about Lu 177 PSMA and then emailed the main authors explaining my clinical situation and asking them if they could offer me Lu 177 PSMA treatment. Four places agreed to treat me and I selected the TUM in Munich.
Write to GP24 in this forum, he knows all the places offering Lu 177 or Ac 225 PSMA treatment in Germany, his Country.
Other trials to search for are theranostic trials using FAPI or bombesin ligands (they do not depend in the PSMA expression), PSMA ADC trials etc.
Hi Philly, My MO recommended to me to not consider “first in human” clinical trials, for example CAR-T PMSA, and stick with more proven therapies at this stage (which may include some phase 2 and 3 studies but not phase 1 studies). Basically, save the “first in human” trials until I’ve exhausted the more proven therapies. I think she based that on my current status. You seem to be in a somewhat similar place as me, that is, metastatic to the bones only and CR? Although CR, I’m still on ADT and an AR inhibitor. I completed Provenge about 2 months ago and about to start Xofigo this week. I haven’t done chemo yet, but plan to start looking for clinical trials to have a plan for after the Xofigo and may consider chemo before a clinical trial. Good luck!
Thanks, but I don’t want to rule out anything based on the definition “established.”There is a good chance I will reach that conclusion but I am trying to clear my mind of pre judgements.
Phase I are not placebo trials. The objective is to test a treatment in a small group of people (typically 20–80) to evaluate safety, determine safe dosage ranges, and identify side effect
Hello Philly and thank you for the info. Cannot offer any help or guidance except we are going through similar time in life. We are heading to MD Anderson Camden next week for more insight Currently with Fox Chase Temple . Your info is a great help to others know we are all here for you. I will let you know what they are offering as treatment option.
If it were me, and I’m prepared for that same situation to occur sometime, I’d opt for radium 223 and Provenge. The two appear to have a synergy and have been in use for quite a while now.
I may try BAT first (my MO is Dr. Sartor) to see if we can get a few more miles out of Xtandi before going that route.
Interesting, I have taken guardant360 test many times. I have talked with their genetic specialist and was told their test only looks at dna not rna— have u been told rna has been added recently?
Xtandi has been shown to reduce cancer growth by 83% in men with castration resistant metastatic prostate cancer. The Xtandi website seems to contradict your doctors' opinions, No.1 in your list.
The problem is that he's already had Zytiga and it's now no longer effective. There is cross-resistance between the Zytiga and Xtandi. The CARD trial showed that second-line Cabazitaxel performed much better than switching anti-androgens.
I can’t believe that it has been 11 days since I posted the note leading off this thread. Time flies when you are having fun. It seems like yesterday that I wrote the post.
The MO from Jefferson called on October 31 to say that there was an opening in a trial for REGN 5678. I reached out on Monday morning to find out how we could get the qualifying process started. I had four exchanges with the office to schedule a conversation. After rejecting a December appointment and then two others late this month, I had a telemedicine conversation on Thursday of last week. It started with the news that I did not qualify since I have not had chemotherapy. Very disappointing.
I am determined to find an appropriate immunotherapy program that I can get into quickly, and have used every networking resource I have to see what is available. In the meantime, I have been approved for Docetaxel, so I can begin chemotherapy if nothing I am doing works.
I will be speaking to an Oncologist at the National Cancer Institute on Tuesday next week. I found a childhood friend that works at the NIH who facilitated this appointment.
I called an MO at MSKCC, where I have previously consulted. At this time, I have an appointment on December 23. That will be too late. They are trying to find space earlier, and his coordinator is supposed to call me back today.
I learned that someone I went to Israel with on a Young Leadership Mission in 1983 is a large donor to the Prostate Cancer Foundation (Michael Milken’s organization) and serves as the Philadelphia liaison. They have all of my information, and I expect to discuss with Dr. Simons soon.
Today, I received a call from my Oncologist at Jefferson who said there is now an opening in the AMG 509 study for December 4. I should be starting the qualification process soon. He said I meet the broad criteria for this study.
I was upset about him not knowing the criteria before calling me last weekend to tell me there was an opening. I sent him a note, expressing my disappointment. I didn’t burn any bridges but got a few things off my chest that I think needed to be said.
I had blood drawn for the Guardant 360 liquid biopsy. It identified an alteration/biomarker called AR T878A. The Dr. at Penn said that information would not influence treatment decisions. The little bit of research I did on the internet so far this morning seemed to confirm that, but there is something about Abiraterone that I don’t understand.
If anyone knows anything about the AMGEN trial called AMG509 or can point me to a place where I can study current information, I would appreciate that.
I have been pushing hard to increase the chances of finding a good program to increase my probability of living with a decent quality of life for as long as possible.
There are a lot of balls in the air. I hope one lands safely where it can do some good. I know there are risks involved but have decided immunotherapy is my preferred direction. I have moved the deadline for making the chemo decision, but decision time is almost here. I had my annual physical on 11/2, and the labs indicate cancerous growth is accelerating. PSA rose from 17.4 to 22.5 and ALP rose from 115 to 157 in slightly more than 2 weeks.
Time for taking action to slow down progression is here.
Hi Philly,Just reread this post. You have the AR T878A marker. Please check out Faith1111’s posts. Her brother has the same marker and he is in trial at Yale with ARV110. It specifically hits this marker and he is doing great with hardly any side effects.
Sorry you didn't get into the REGN5678 trial? I am starting preliminary testing for it at Columbia tomorrow. I did not have chemo, but did have failure after 2 different treatments of Zytiga (6 mos) and Olaparib (2yrs). Am BRCA2+.
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