clinical trials

GloHo

@Sandi6

It was so nice to meet you and hubby in person and to be able to chat face-to-face. You look very healthy and happy and that curly hair suits you! Congratulations, again, on your 1-year milestone. 

After chatting with you, it dawned on me that your journey from diagnosis to clinical trial is very different than mine and I was wondering if you would be comfortable sharing your journey with us?

GloHo

A STUDY OF THE PKMYT1 INHIBITOR RP-6306 IN COMBINATION WITH CARBOPLATIN AND PACLITAXEL FOR TREATMENT OF RECURRENT TP53 OVARIAN AND UTERINE CANCER (GYNEREP)

PHASE 1/2 (21-DAY CYCLE)

6 CYCLES ONLY

CYCLE 3

So…Cycle 3 was delayed because my neutrophils are too low.

We are trying to arrange treatment for next week. Chemo does not have a chair for me so I am on a wait list and will find out Thursday or Friday when they can fit me in. Of course, there is no guarantee my count will be up to trial requirements by next week, so not sure what will happen in that case. Maybe an injection or another delay?

In the meantime, I’ll share some of my other results with you.

White blood count is very low but was not a determining factor in the delay.

B12 has increased to just above normal. Dr recommends I continue with the supplement to bring the count up more.

CA125 decreased again. It went down 1300.

Biopsy Pathology Report indicates that there is dead tumour tissue or, as they put it, background necrosis suggestive of treatment effect.

CT Chest report is stable - no pleural effusion, no new progressive disease.

CT Abdomen/Pelvis also reports stability with decreased ascites.

My thoughts

Overall, positive reports and it appears the meds are keeping the disease stable.

From previous experience on these drugs, I was expecting issues with my neutrophils and platelets, just not after Cycle 2. My platelet count seems to be remaining stable which is good and one less thing to have to worry about.

The Dr goes through my entire blood report with me and explains why they are not concerned with some of the counts. They can tell they are a result of the meds and that there is no damage to my organs. Amazing!

Delays are always a concern and difficult to deal with for many reasons.

1. There is a break in the treatment schedule.

2. I have to wait for a last minute chemo booking and try to make accommodation arrangements because I travel to Toronto for treatment.

3. A delay changes everything in your personal calendar, including medical appointments my husband has, fun things that you already booked around your current schedule have to be cancelled or rearranged.

4. Holiday planning with family and friends…Christmas is coming!! This delay may actually work in my favour since I had a treatment scheduled for New Year’s Day that will now be pushed to the following week and it won’t interfere with Christmas either.

I mention the delay issues because the nurse and Dr were like…we have to delay. There was no indication that they thought you had a life or anything better to do outside of your cancer schedule and how much the delays affect your life!! While there is nothing that can be done about it, I just felt like they didn’t have a clue. On the other side, you have to be flexible and prepared for these things as best you can. Delays do happen.

GloHo

@Tanja

In response to your post in Let’s Get Started (copy and pasted at the end of this post)

You have obviously done a lot of research and the information you have provided is very informative and helpful.

You are correct that it takes courage and is a very personal choice to participate in trials.

I am glad that my posts have provided you with a nudge to look into clinical trials. When I began my journey, I did not find specific info on trials on the site and decided I would journal my personal experience. Each trial is different, there are many differences and some similarities. It was my hope to present info so that anyone considering a trial would see the process, the scheduling and the time commitment required (especially for us out-of-town participants).

The trial database I usually use is https://clinicaltrials.gov/ . Have you used that database? This site has a filter so you can choose “recruiting and not yet recruiting” so you don’t get trials that are completed.

I obviously want to find something that will work for me but also believe that my participation may help someone in the future.

I told my Onc from appointment number one that I would be interested in doing a trial and at each visit I would ask if anything was available and/or present trials that I had found and thought I might be eligible for. I noticed after a few visits that my Onc proactively started doing trial inquiries on my behalf before each of my visits and was prepared for my inquiry 😁. I just realized that this is where I began proactively self-advocating for my care and I have never stopped 🤣.

I am currently on my 8th treatment and this is my 3rd trial 😁. I am determined!! I did my first trial at 4th line of treatment.

I have also had 4 biopsies. I mention the biopsies because there is some marker info included in the pathology report. Interestingly, each of my reports at different stages of my disease came back with a couple of the same and a couple different markers. My results did not show anything out of the ordinary for HGSOC so no specific marker for targeted therapy.

Speaking of markers…I totally agree that this testing at the outset would be beneficial!

There is a study called Study looking at Biomarkers in Ovarian Cancer (BioDIVA). It is a very extensive biomarker testing study. In addition to a blood draw, a tumour biopsy is required. The study indicates it is for high-grade serous. We have different cancers and I’m not too familiar with clear cell…does it fall under high or low grade? In any case, it may be worth an ask about this specific study. It is available at several cancer centres across Ontario. Now, the results do take time…and I would not put an eligible treatment on hold waiting for the results. If anything pops for targeted therapy, and if there is a trial available for that specific marker, discuss course of action with your Onc.

Now, also worth a mention here, is the genetic component of this testing. This is a tough one because you have to decide whether or not you are going to share these results with others who may be at risk for hereditary disease [siblings, children and grandchildren (both male and female), cousins, nieces, nephews]. A genetic counsellor is available to help you work through the complexities of this decision.

Even if you have had the biomarker testing, each trial will also do their own testing. I have had blood, CT, ECG, ECHO, and/or biopsies to determine trial criteria eligibility at time of registration for the trial.

Still alive and functioning 🤣. I think this amazes me the most! I was cancer naive when diagnosed and really didn’t know what to expect - I was scared, sad and angry. I am, after 5 1/2 years, still considerably well. I do not have symptoms or pain and I have experienced very few side effects to all of the drugs I’ve had thus far. It is a difficult journey and, when I hear that a drug is not working and there is progression, like you, I wonder what’s next and how long (or if) it will work. When I get this news, I have to admit there are tears and feelings of anger. I let myself feel whatever emotions I have, internalize my reality, and then I am able to move forward. I usually have a positive outlook and continue to keep the hope that treatment will, at the least, stabilize my disease for a while.

As @Alwayslearning says “Knowledge is power” and I hope this missive imparts some knowledge that will lead to personal empowerment throughout your journey. There is also power in numbers and this site is truly amazing in its simplicity at bringing us all together - to ask the tough questions, to share our experiences and wisdom, and to offer support to each other.
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TanjaNovember 1

@GloHo I just read your clinical trial story…. Very impressive and what strength to make it through all the up and downs. This gave me courage. I forgot under which subsection I read it, so I wanted to text here ( the site with all the sub topics is a bit confusing). I checked for clinical trials at PMH and Buffalo, US and learned pretty fast that it is difficult to get into these trials - eligibility, trials are ended, or- US - too expensive. It is also very encouraging that you are still alive and functioning. I am always worried that if drugs don't work, the end is in near sight.

I am in 2nd Carbo and paclitacel + Beva cycle for OCCC (Tp53 positive) recurrence and equally already look for clinical trials as I am expecting becoming platin-resistant any moment. I had a good talk with my MedOnc at PMH. Similarly to an earlier comment by someone, I remain shocked by my experience so far that tumor genetics and testing is done on a need-to-know basis. 

So, when I had the discussion about newest and best trials for my clear cell tumor, I learned the following that I want to share: It appears that immune therapy works best for those with MMRd - mismatch repair deficiency. And I read somewhere that this is because these tumor cells look more foreign to our immune system. Since, I am proficient, meaning I don't have MMRd, immune therapy is not a good option for me. My hope that immune therapy could rescue me in the future was immediately destroyed- but then who knows what will be developed in the future. It appears the antibody -drug- conjugates - ADC are the new kid on the bloc. These drugs consist of an antibody that targets a specific protein that is over expressed in your tumor. This antibody is linked to a strong cell toxin which is released when the antibody docks onto the protein. Since the tumor has more of it, the idea is that the tumor gets more toxic drugs than the rest of your body. On such famous drug is Mirvetuximab directed agains folate alpha receptors.

In respect to my tumor, she mentioned to test it for HER2- human epidermal growth factor receptor 2- which can be expressed in all solid tumors , also in ovarian cancer. As per literature, it is associated with poor prognosis. Apparently there is now a ADC against HER2 which is trastuzumab deruxtecan. After the discussion, I thought why wasn't this tested earlier. It is not a mircacle drug but can stabilize disease and prolong progression free survival. The more I think about it, we should all be tested for all therapy and prognosis - relevant markers, right at the beginning and then treatment should be immediately tailored to this. I guess, the problem is that we don't have miracle drugs..




Sandi6

@GloHo it was so lovely meeting you in person. Always great to have an authentic conversation.
My move from my local hospital, in London, to a clinical trial at PMH was not straightforward.
My oncologist explained that I was full of cancer, the frontline treatment isn’t working, so I wasn’t given the 6th dose. He also told me that I wouldn’t live more than a couple of months and I would be referred to a medical oncologist.

Feeling stunned and overwhelmed, I frantically researched for options!!! Fronds had been raving about PMH for months so I researched their referral process.
I then called my family doctor and requested a referral be made for a clinical trial at PMH. It was only a few days until I had an appointment.
im grateful for the opportunity for a longer life. Loving every minute of it.

We really need to advocate for ourselves, and quickly as time isn’t necessarily on our side. I’ve been diagnosed with ovarian carcinosarcoma which is very aggressive so time is important!

Wishing everyone healthier days ahead 💕

Strongwoman

I hear you @Sandi6 about the time is precious. I have been given the same prognosis except with no back up plans available to me, After tears and wrapping my head around it, I take every day for what it is, I hope you will too with time. They are hard pills to swallow these ones and we hope they are wrong but never know. Live every day to the fullest as you can is my motto. I hope you will get there too, Wishing you the best as you recover from your recent news.

GloHo

A STUDY OF PKMYT1 INHIBITOR RP-6306 IN COMBINATION WITH CARBOPLATIN AND PACLITAXEL FOR TREATMENT OF RECURRENT TP53 OVARIAN AND UTERINE CANCER (GYNEREP)

PHASE 1/2

6 CYCLES ONLY

CYCLE 3

Blood counts all back to normal…treatment is a go.

CA125 decreased by 7300! That's a total of more than 50% from trial start to post-Cycle 2.

Unfortunately, I had a reaction to Carboplatin and infusion was stopped. I experienced nausea (no vomitting), diarrhea and face flushing. The nurses administered meds to counteract the reaction.

The Onc has referred me to an allergy clinic at St. Mike's to test for Carboplatin allergy. As of today, I have not heard from the allergy clinic. I have alerted my nurse and she is going to speak to the Onc.

I am also experiencing severe sensitivity to Benadryl. I negotiated a single dose for this infusion. Given my reaction, that was perhaps not the best idea, but my sensitivity to Benadryl is debilitating so I wanted to give it a try. Part of the problem is that I do not have enough time to sleep off the effects of the Benadryl after a half hour infusion of Carboplatin so I am very much under the influence of Benadryl. After reflecting on how I felt after this infusion, I realized that I either blacked out or was so tired I don't remember some things when I left the chemo unit. I do not remember leaving the chemo unit and boarding the shuttle for PMLodge. I fell asleep on the shuttle and someone woke me when we arrived at the Lodge. I do not remember going from the shuttle to my room. I do remember being in my room and lying down to sleep. I slept for 2 1/2 hours. When I woke, I had a bite to eat and then went back to bed and slept until morning.

So, for Cycle 4…the following is what is on my mind…

• how much Carbo did I get before my reaction to the last infusion?
• will my blood counts be okay so there is not another delay in treatment?
• what is my Onc going to recommend as the go forward given my reaction to Carbo?
• allergy testing has not been done yet - can we move forward without it?
• the Benadryl issue is serious to me…I need to get that across to the Onc! I am hoping there is an alternate, but they have been pretty firm on keeping Benadryl (part of that was because it was in the trial protocol but I think that requirement has been lifted now).

I do not seem to be having any reaction to the oral trial drug (RP-6306).

I am fatigued, tired and weak for about a week following infusion, but that is how I reacted to the Carbo/Taxol combo last time. I am not experiencing anything out of the ordinary. My appetite has been quite good with little to no nausea (if there is any, it is in the week following infusion and is not severe - no meds required).

mcb

@GloHo that is an amazing drop in CA125! It was incredibly high to begin with. I had a similar reaction to Benadryl but only on the 5th cycle, the 6th was back to the usual fidgets and drowsy. I was getting Benadryl as slow IV over 30 minutes then 30 minutes before starting Paclitaxel. Maybe it won’t happen to you every time. Still, I wouldn’t want you leaving unescorted.

GloHo

A STUDY OF THE PKMYT1 INHIBITOR RP-6306 IN COMBINATION WITH CARBOPLATIN AND PACLITAXEL FOR TREATMENT OF RECURRENT TP53 OVARIAN AND UTERINE CANCER (GYNEREP)

PHASE 1/2 (21-DAY CYCLE)

6 CYCLES ONLY

CYCLE 4

Blood counts: The majority of my blood counts are okay and are actually improving with each treatment - although still not in the normal range.

Neutrophil count was right on the cusp of low – phew – just avoided a delay!

CA125 decreased by 4000! That’s a 75% decrease after 3 cycles!

Pre-meds: The following adjustments were made to my pre-med schedule to try to avert a reaction to Carbo.

• added oral Dexamethasone 12- and 6-hours pre-infusion
• added oral Cetirizine (Reactine) evening before infusion
• added oral Montelukast evening before infusion
• slowed infusion (1/2 hour to 1 hour)

These drugs were prescribed in addition to the regular pre-meds I take (Emend, Ondansetron). 

Infusion: Unfortunately, I did have another reaction about halfway into the infusion – nausea and face flushing. However, I was able to alert the nurse as soon as I started feeling nauseous and we were able to avert the diarrhea that I had the last time. The change from Benadryl to Reactine meant that I was more alert and aware of my reaction sooner.

Option: The chemo unit Dr dropped by to discuss my options following my reaction. I had received 1/2 of the Carbo dose before my reaction and was given the option to continue the infusion once I was stabilized. We discussed the likelihood that I would have another reaction and the potential that the reaction could be more severe. He did indicate that my reaction would likely not be severe but it could happen. My gut told me that it didn’t make sense to continue the infusion with a drug I know I am sensitive to and suffer another reaction. I decided that I would not rechallenge Carbo and end my infusion. 

Allergy Testing: The Dr referred me for allergy testing (St Mike’s Hospital) for Carbo and Cisplatin. Although we know that I am sensitive to Carbo, the test mayshow my level of sensitivity. I am hoping that I do not also have a sensitivity to Cisplatin. Cisplatin is the only alternate to Carbo allowed in the trial.

Allergy Results: Negative. I am not allergic to either Carboplatin or Cisplatin.

My reaction is caused by a sensitivity. It will be up to my Onc and I to determine whether or not I move forward with Carboplatin with another adjustment to pre-meds or if I am given Cisplatin as an alternate.

It is nice to know that I do not have an allergy to either chemo. This opens the door for potential use of Carbo again or Cisplatin in the future.

NEXT STEPS

CT scan is scheduled following this treatment.

Discuss next chemo infusion options with Onc.

NOTES

Benadryl Sensitivity

I was able to self advocate for the change from Benadryl to a 2nd generation antihistamine, Cetirizine (Reactine).

The nurse was impressed that I was able to negotiate the change from Benadryl to a 2nd generation antihistamine. He indicated that most Drs will not agree to the change. Given my hyperreaction to Benadryl - I had some black out periods following my discharge from the hospital after the last infusion - I was finally able to convince the Dr to make the change. I understood that Benadryl was written into the protocol of the trial for Cycles 1 and 2, but I had hoped that the change would be made in Cycle 3. It was not and that is when I realized I had black out periods following my discharge from hospital. It was very scary when I reflected back and realized this! I know a lot of patients experience drowsiness from Benadryl and I guess the Dr is so used to hearing this complaint that she just put it aside as a normal reaction. It was very frustrating trying to convince the Dr that my reaction was not normal. 

This change made a huge difference in my ability to stay awake and converse with the nurse about how I was feeling and to ask questions about what drug injections they were giving me via IV to try to lessen my reaction. I did have a reaction again but I was able to alert the nurse earlier in my reaction because I was not knocked out with Benadryl. I caught this reaction at the face/neck flushing and nausea stage (no diarrhea). 

I also have Benadryl listed in the allergy section of my health portal. Not that I am allergic to it but I am hypersensitive and want the opportunity to discuss my reaction with my health care team. 

The Reactine (Cetirizine) still caused some drowsiness and I dozed off in the chair but when the nurse had to wake me, I woke with a clear mind and knew what was going on. 

GloHo

A STUDY OF THE PKMYT1 INHIBITOR RP-6306 IN COMBINATION WITH CARBOPLATIN AND PACLITAXEL FOR TREATMENT OF RECURRENT TP53 OVARIAN AND UTERINE CANCER (GYNEREP)

PHASE 1/2 (21-DAY CYCLE)

6 CYCLES ONLY

CYCLE 5

Blood counts: The majority of my blood counts are still improving with each treatment - although still not in the normal range.

Neutrophil count was right on the cusp of low again – avoided a delay!

CA125 decreased by 2000! That’s an overall decrease of 90% after 4 cycles!

My Onc was impressed with the decrease in CA125 given that I had not received full dose for the previous two infusions - 2/3 dose (Cycle 3) and ½ dose (Cycle 4).

CT scan results: The scan showed some decreases, no new and no progression. Overall, my tumour burden has decreased by 23% and has been deemed stable. In order to be diagnosed as partial response, the decrease has to be 30% or more.

Infusion discussion: Given my negative allergy results, the Dr would like to treat me with Carbo again. However, she would like to increase the pre-med schedule to a few days prior to treatment. This means that for this cycle (since I only have one day before treatment), I will only be receiving Paclitaxel.

I did give some pushback about missing Carbo this treatment, but she explained that if I have another reaction, I will be out of the trial. Three reactions are the limit. We agreed that getting Paclitaxel only this treatment is better than delaying treatment.

Pre-meds: Since I will only be receiving Paclitaxel this cycle, Ondansetron is the only oral pre-med required.

Infusion: All went well.

NEXT STEPS

CT scan has been scheduled following this treatment.

Pre-meds (Cycle 6) schedule has been adjusted to increase the length of time before Cycle 6 treatment to pre-dose with appropriate meds to try to offset my reaction. This last treatment will include the increased pre-med schedule along with Paclitaxel and Carboplatin infusions.

Rechallenge option (Cycle 6): If I do have a reaction and am given the option to reintroduce Carbo after they stabilize me, I will be opting to go for it this time.