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Well folks, here I go again!! A new trial!!

CX-5461

Phase 1 study to find the right dose of CX-5461 and to look at what effects CX-5461 have in patients with solid tumours with BRCA2 and/or PARB2 mutations

Cancers included in the study: pancreatic, ovarian, prostate and breast cancer

First, although I do not have one of the two mutations identified in the title, I do have a mutation, NBN, that is included in the main group of this study. A special shout out to the Fellow who was working the day I went in to explore trials!! I was already assigned this trial, but he recognized the mutation and went to confirm that it was, indeed, a mutation being explored for this trial. I have to say, it provided some relief to know that I had two specific things for this trial.

This is a phase 1B study so it is still in the early phase and does not mean the drug will target the mutation but at least it is being explored and may help those that come behind me. On a more positive note - and with "hope" - the drug may be exactly what I need!! 

I am just moving through the screening process now and will continue to journal my experience.

@GloHo  Wonderful news!  Keep us posted!

CX-5461

Phase 1 study to find the right dose of CX-5461 and to look at what effects CX-5461 have in patients with solid tumours with BRCA2 and/or PARB2 mutations

Pre-screening process 

Meet with the Dr to review trial recommendation.

Meet with the trial coordinator to discuss tiral requirements and sign documents to begin the trial screening process. 

There is a 28-day (or less) window to complete all required tests to determine if you meet the criteria for participation.

Screening tests

Blood

CT 

ECG 

Heart test (MUGA) - a small amount of radioactive tracer injected

Eye exam (external eye clinic - costs covered by trial)

Biopsy 

Results

Heart test: Borderline abnormal 

I'm sure the Dr will discuss these results with me. I am not too concerned as the ECG done during this procedure was fine. I did fall asleep, twice!, during the test. That may have contributed to a couple of blips during the test?😂 In any event, they did not ask me to return for further testing which, according to my coordinator, is a good thing.

Biopsy: I opted for local freezing only, no sedative. I had 7 cores taken - one for clinical and six for the trial. Some of the trial cores may be for the three genetics studies I am participating in! One core will be sent to pathology and will reveal any genetic changes. The Dr has also indicated that she is going to test my FRa status from this tissue to see if I qualify for Elahere compassionate use.

The ultrasound monitor broke down during the procedure and they had to switch it out.

I did not experience any pain following the procedure and there is only a small bruise at the puncture site. 

CX-5461 known side effects

Usual - fatigue, nausea, etc. 

Eye - photosensitivity to UV rays

Skin - whole body photosensitivity to UV rays

As you may have noticed, sun sensitivity is the main side effect. 

This means that I will have to avoid direct sunlight and be covered from head to toe, LITERALLY, when I am out and about. 

It's funny…tell me you're going to inject all kinds of poison into me and I don't blink. But tell me I have to avoid the sun and I hesitate. It will certainly be interesting and challenging!

The trial provides 

Sunglasses (wear over)

Hat

Jacket or hoodie

Gloves 

Sunscreen/lip balm (replenished each cycle)

UV-rated clothing

I decided to look for protective clothing. Much to my surprise, most sports store sell this clothing for runners, swimmers, etc. I found some pants, on sale!, so picked up a few pair. I am now looking for some tops - not in many stores yet…will check in a couple of weeks. I was just at Winners for something else and found a couple of UV-rated tops there! I am also looking for swimwear (full coverage) - we have an aboveground pool that provides much relief during the hot summer months. You can, of course, order all this stuff online but I like to see/feel what I am getting.

My team

The trial team has been phenomenal! My emails (questions) are answered promptly and information regarding test requirements were provided in a clear, concise email. I feel like I am well-supported and can reach alternate contacts should the need arise. 

Reimbursement

The information package indicated the trial would reimburse travel and parking costs. I am an out-of-town patient so this is of interest to me!! However, when I asked my coordinator to follow up with them for specifics, she said they would pay $35. So now I have lots of questions about what that means. I plan on sending a little note with my first reimbursement submission explaining what costs are associated for my participation in this trial as an out-of-town patient. We'll see what comes of that. Some trials do not cover any costs, so even a little something is welcome. I don't know how they arrive at the amount - that would not even cover parking or taxi/uber if you were local. 

Vaccines

While I was on my chemo holiday, I decided to get caught up with all of my health vaccines (COVID, flu, shingles #1). I have to go back for shingles shot #2 within 6 months which will be during the course of this trial. I asked about this and I will be allowed to get it but I will have to coordinate it according to my treatment schedule. Makes sense and am thankful that I will finally be able to complete my shingles vaccine. 

Next steps

Next Tuesday I have pre-treatment blood/urine/ECG tests and an appointment with the Dr. We will review my tests results at that time and they will advise if I meet the criteria to participate in the trial. 

In preparation for an okay to move forward on this trial, there is a chemo chair already reserved for next Wednesday (Day 1) and the following Wednesday (Day 8).

🤞🤞🤞

CX-5461

Phase 1 study to find the right dose of CX-5461 and to look at what effects CX-5461 have in patients with solid tumours with BRCA2 and/or PARB2 mutations

I have been approved to participate in the trial!

Treatment schedule 

28-day cycle

2 weeks on, 2 weeks off

Treatment on Days 1 & 8

Cycle 1

Pre-Day 1: Blood \ Urine \ ECG \ Dr 

Day 1: Blood + Dr + Ondansetron pre-med (1/2 hour) + Treatment (1 hour infusion) + Observation (1-hour) + ECG (in chair)

Days 2-6: off

Day 7: Pre-Day 8 tests - blood, Dr 

Day 8: Ondansetron pre-med (1/2 hour) + Treatment (1 hour infusion) [no ECG, no observation]

Days 9-27: off 

Pre-treatment med: Ondansetron (anti-nausea med)

Participant Sun Exposure Diary: A daily diary is to be completed indicating that sunscreen is applied and reapplied, indoors and outside, total sun exposure each day (approximate) and any other uncomfortable skin or eye side effects. The nurse also asked me to note the time when Ondansetron is taken each treatment day. 

Other on-treatment tests/schedule

CT: every 8 weeks

ECG: every pre-Day 1 + one hour after each Day 1 infusion

Eye exam: every 8 weeks

Biopsy: when trial ends/progression

Cycle 1 complete!! But not without some issues. 

Side Effects

I did not experience any nausea or additional fatigue. 

A potential side effect is hand-foot syndrome.

Another potential side effect is mouth sores. 

Eye sun sensitivity is another concern while on this drug. Sunglasses are provided and there are eye exams every 2 cycles. 

This drug makes me extremely sun sensitive and even though I donned all the UV protection garb, I managed to get sunburned after my first treatment!

Bottom lip, swelling with blisters…ouch!! I am currently trying to heal my lip and found that Eucerin Aquaphor Lip Repair is providing relief and, hopefully, healing. I tried some other lip treatments but they just didn't cut it for me. 

I am now thinking of a way to ensure I have extra protection for my lips in addition to the SPF lip balm. I think if I wear a mask under the hat mask when I am going to be out in direct sunlight for a period of time that should do the trick!

My left hand had some redness across the knuckles. My right hand was sunburned on the top of the hand with redness and some swelling. As well, 4 of my fingernail beds have turned dark. I think the hand burn was a result of driving (steering wheel) even though I had applied sunscreen and was wearing the UV gloves. The Dr prescribed a cortisone treatment for the hands. 

For my hands, while driving, I may resort to wearing a light pair of winter gloves over my UV gloves. 

The Dr had to contact the trial sponsor to inform them of my issues. She indicated (warned me) that the sponsor may want to reduce the dose for Day 8 and moving forward as a result of my reaction. Fortunately, the dose remained the same for Day 8 and I have extra incentive to ensure I am doubling up my protection so I do not find myself in this position again. 

Since I had these side effects, the Dr has scheduled a telephone appointment in a week to see how I'm healing and if there is anything new.

I am again travelling to Toronto from London and staying at the Princess Margaret Lodge from Monday to Thursday each treatment week. 

I am now off treatment for two weeks. YAY!!

Notes

As someone who has never had an issue with sun exposure - I tan very easily - this new way of protecting myself has been an experience! I am slowly getting used to having to take the time to ensure I am sunscreened and wearing my protective gear before I go outside. 

The last time I had hand-foot syndrome and mouth sores was after my third treatment of another drug...so, I am waiting to reach and hopefully surpass that milestone without any issues while receiving this drug.

From past experience with hand-foot syndrome, I am applying Eucerin Complete Repair Plus moisturizing lotion with 10% Urea on both my hands and feet when I go to bed. There are many other suggestions on this site if you want to explore potential precautions/remedies for this syndrome.

I am doing a salt water rinse before bed each evening to try to ward off mouth sores. If I do happen to get mouth sores, I know the prescription magic mouthwash will take care of it. 

For the sunburn on my hands, the Dr prescribed Betaderm ointment (.05%). Directions indicate to apply twice a day for seven days. So far, this ointment seems to be doing the trick. 

For the sunburn on my bottom lip (with blisters), I am applying Eucerin Aquaphor Lip Repair very frequently throughout the day. This product provides some cooling when applied, moisture for awhile, and it seems to have healing properties for my blisters and sensitive lip where skin now has to be renewed. I have to be careful what I eat so that I don't irritate my lips (i.e., no acidic or salty foods, etc.). This is not an SPF product, so I still have to apply SPF lip balm when I go outside to ensure I have sun protection. It is difficult to find an SPF product that does not irritate my sore lips (perfumes, flavourings). I usually use Blistex products for my lips and found Blistex Ultra Protection with SPF 30. This lip balm feels good on application and I do not get that tingly ouch when I apply it to my sore lips. 

CX-5461

Phase 1 study to find the right dose of CX-5461 and to look at what effects CX-5461 have in patients with solid tumours with BRCA2 and/or PARB2 mutations

Treatment schedule 

28-day cycle

2 weeks on, 2 weeks off

Treatment on Days 1 & 8

Cycle 2

Pre-Day 1: Blood + Dr 

Day 1: Ondansetron pre-med (1/2 hour) + Treatment (1 hour infusion) + Observation (1-hour) + ECG (in chair)

Days 2-6: off

Day 7: Pre-Day 8 tests - blood + Dr 

Day 8: Ondansetron pre-med (1/2 hour) + Treatment (1 hour infusion) [no ECG, no observation]

Days 9-27: off 

Participant Sun Exposure Diary: Complete

Cycle 2 complete!!

Side Effects

Fatigue

Bottom lip sensitive

Hot flashes!! New to me

Upcoming tests

CT (week 8) This will be my first CT since I started the trial. I am anxious to see the results.

Eye exam (week 8) This will be my first eye exam since I started the trial. I have not noticed any deterioration…it will be interesting to see the results.

Notes

CA125 has been rising. I expected a rise at pre-cycle 1 since it had been a couple of months without treatment. I was hoping not to see an increase in cycle 2 but, alas, there it was.  So, it looks like this treatment is not working for me. I will speak to the Dr this week about it. Maybe it takes a few cycles to kick in?🤞  

Side effects are manageable although the fatigue is constant with a couple times throughout the day where I may need to nap. 

Sun gear: With the current heat wave, wearing the sun gear is like wearing a sauna suit!! I am getting used to having to cover up every time I step out the door.

Palliative Care referral: Spoke to the Dr. He made a couple of suggestions, is sending a note to my GP and suggested I follow up with her.

Supplements: I am taking B12, iron, vitamin D and a multivitamin. I have been finding it difficult to maintain a consistent schedule and know that in order for these to be effective I have to take them on a regular basis. For the last week, I have finally found a schedule that works for me. Here's hoping I will see a benefit🤞. Really hoping this will help with fatigue. Time will tell.

Thanks so much for the update, GloHo.  Hopefully, the increased CA-125, is to be expected and it will start decreasing soon.  Take very good care of yourself, Sheryl

@GloHo I cross my fingers for a good CT result! Thx for the details in update. I feel for you.

@GloHo thank you as always for sharing your trial information. I too hope that the rise in the CA-125 is an expected outcome and further treatments will see a decrease. Glad you were also able to find the supplements schedule. With so many things going on, it can definitely be difficult to figure out timing etc. I and other definitely understand that. 

You are a strong Teal Warrior. Sending nothing but positive vibes your way for the upcoming CT scan.

CX-5461

Phase 1 study to find the right dose of CX-5461 and to look at what effects CX-5461 have in patients with solid tumours with BRCA2 and/or PARB2 mutations

Treatment schedule 

28-day cycle

2 weeks on, 2 weeks off

Treatment on Days 1 & 8

END OF TREATMENT

Well…that was a quick trial!!

Eye exam was normal.

CT scan showed definitive progression and some new nodules.

CA125 showed significant increase.

Blood work was off a little on almost all counts. I did get it done at a different time of day and on my travel day so maybe that made a difference? Nothing concerning but it was interesting to see.

Meeting with Onc

Given the combined CT and CA125 results, I was pretty certain that I would be removed from the trial. That decision could not be made until the Dr received the report from the trial technician. Interesting to note that the trial techs do a thorough review of every scan and do measurements of everything seen in the scan. So, I was not surprised with the decision to end the trial. The drug is obviously not working for me.

End of trial requirements

• Immediate blood work
• Immediate ECG
• Complete sunshine log for another month
• Sun cautious for another three months
• The trial would have liked a biopsy at this point but I opted not to undergo another biopsy at this time.

Next steps

One-month follow up appointment and some telephone follow ups in the future.

NOTE

This is my personal journey. It does not mean that it will not work for you! I met another OC patient on this same drug who has experienced disease stability for the past 7-8 months!! 

What's next for me?

Well, surprise, surprise, I still have options. Yes…plural!!! I was not expecting that at all.

Option 1: Elahere

• more on this option below

Option 2: Arc101 Phase 1 trial

• more on this option below

Option 3: Phase 1 trial

• testing drug on many different cancers to determine which cancers react best
• referral to Phase 1 team is on hold until other options are exhausted

Option 4: Gemcitabine

• the second last standard of care drug I have left

Let's get to my Elahere option!! 

I know you will all be interested in hearing the ins and outs of this one! 😁

I am not eligible for Elahere as per their criteria…even if I'm FRa positive. I do not meet the 1-3 prior lines of treatment…way over that count! However, the team has given me hope over the last few months that there are avenues to explore that may result in getting this treatment.

At my last biopsy, because Elahere is on the horizon for use in Canada, my Onc took a tissue sample for FRa testing. My results are in and I am FRa positive (happy dance💃!). I am in the 20% who test positive. I was definitely not expecting this result…couldn't believe it!!

A fellow I had a couple of months ago indicated that they were submitting a compassionate treatment request to Elahere…of course my FRa status would have to be positive for them to even consider me.

I also just learned that there is an opportunity to request permission from Health Canada for Elahere even before they approve it. My Dr referred to this as a "unique" trial. I guess for people like me, running out of options and need it now?! I had to sign a form giving my team permission to make the request. I also need to do an eye exam as part of the approval process to begin Elahere. I believe the Health Canada approval process may take 3-4 weeks.

The two submissions for Elahere will continue even if I do opt for the trial. Time is not on my side so I need to make a decision fast!! The Dr indicated that she thinks I should start a treatment as soon as possible and not wait.

ARC101 Phase 1

• focus on gyne cancer only
• a potential best-in-class T cell engager
• targets solid tumours expressing Claudin6 protein
• as I was preparing this note, I received a call from PMH saying the trial just opened and I am eligible - would I like to participate?

Good grief! Now I have to figure out whether I should wait for Elahere approval - which I may not be granted - or start the phase 1 trial immediately.

I am leaning towards doing the ARC101 trial. My thought process…

I do not have the Claudin6 protein but one of my pathology reports indicated I do have Claudin4 (there are 27 different Claudin proteins). Claudin4 is an indicator of more aggressive behaviour. In reviewing the research about ARC101, it indicated that this drug has no off-target binding and avoids other Claudin family proteins. So…huh…what do I do?

• because Claudin6 has not been noted may not mean that I don't have it, it's just not overexpressed in my tumour?
• this trial is focussed on gyne cancer only
• this is a true phase 1 start for me -  trial dosing, side effects and adverse events. I usually start participation when the phase 2 dose has been determined and some of the side effects and AEs are known.
• I will know at my 8-week CT scan whether or not this drug is working
• I will have CA125 tests to indicate which way I am headed
• I can stop the trial at any time (if I happen to be approved for Elahere and there's no wiggle room to delay the start)
• maybe things will all align at the right time

It is a bit scary having to wait given my progression but I have to wait a 28-day washout period anyway and I'm already halfway through that so I will be ready to go with whichever option is available. 

Knowing that I have a few options definitely relieves the stress.

I have always asked what's next when I start a new treatment because I like to plan ahead, research and just be prepared when the time comes to make the switch. I think this way of thinking and self advocating has helped me to remain hopeful and positive. I do not dwell on the unknown…I always know where I am headed. Ha! Unless they switch it up on me…like they just did 😁.

The Dr said they were going to set up an appointment for me next week to further discuss the trial. Both the Dr and trial coordinator will be at the appointment so I will be able to ask questions on both the Elahere and trial scenarios. I have a lot of questions 🤣.

It looks like the bottom line for me is that I just do not have time to waste!! I do not know how much longer I can go without some positive results. That brings me back to Gemcitabine which has been shown to provide a few more months of survival. Can I start Gemcitabine then stop to begin something else even if it is working? If I do stop Gemcitabine can I go back to it? What if it doesn't work for me? That will leave me with my last standard of care option…Topotecan.

Thank you all for listening. This was all a jumble in my head and having the opportunity to put it in writing and try to make sense of it all has really helped me focus, make a decision and just get my head wrapped around exactly where I am in my journey.

Now I wait for my appointment!!

@GloHo you remind me of that song "Tubthumping" by Chumbawamba. Lyrics, "I get knocked down, but I get up again. You're never gonna keep me down."

What a Teal Warrior you are. I'm beyond thrilled that there are options. I love the pluralization of that word as well. Plus the information you continue to share just shows how much is available out there. While it may not apply to all of us based on our personal situations, it certainly gives an air of hope.

Can't wait to hear what the doctor has to say. I'm so glad the doctor gets you in so quickly to discuss. That I'm hoping, alleviates some stress as answers and information will come more quickly.

Sending you positive vibes and hugs.

#Clinicaltrialsandresearch

@Alwayslearning

OMG…haven't thought about that song in a while…but it has rattled through my brain a few times throughout my journey 🤣🤣.

It is amazing how quickly they move you through things at PMH. It certainly does lessen the stress and anxiety experienced when you have too much time to wait for the next step. 

@GloHo. Thank you for including us in your pathway and thoughts. Wow - great to hear that you have options. Both, Elahere and Arc101, sound like good options. If you have some time left, then I think these 2 options may offer you halt or some reversal of the disease. I am always worried that the standard of care drug is only given when nothing is left. The Oncologist at Buffalo told me that in the recurrence platin -resistance OC setting, the NCCN, the National Comprehensive Cancer Network, believes that the best management is clinical trial and only if not eligible, then standard treatment. But of course, this depends on your individual setting and how much time you have left.
If you can get your hands on Elahere, great, I hope that your Oncology team can pressure Health Canada, but maybe the compassionate use is an option, too, maybe as a bridge. I am on compassionate use of Bevacizumab as I insisted on some maintenance treatment. I got a bit lucky as one company agreed, others denied. As you said, advocating for yourself is key.
I asked for alpha-folate receptor testing at the beginning of the year, but it was not available outside of the trial, and I have the wrong tumor. So, again amazing that you got a result and your positive.
I have heard about Antibody-dug conjugates against Claudia 6 and BionTech combines CART-T against claudin 6 with amplifying RNA vaccine - so there is some belief that this might work against solid tumors.
I cross my fingers for you. Maythe cards continue to play out your way. Hang in there!

@Tanja

Thank you so much for your continued support. I love your analytical mind and the way you can decipher all those medical reports…and then share with us the Cole's Notes version 😁. I really appreciate hearing about the things you uncover in your research.

I was reading the prescreening paperwork and this trial is focussed on Claudin6. So my hope is that it is present in my tumours. It's a possibility. This drug also attaches to T-cells to help the immune system fight the cancer. So, there's that too.

I am not getting my hopes up with this one…cautiously optimistic. I really have to find out why my Onc thinks this is a good fit for me.

It's interesting that you mention the order of treatment. A lot of Phase 1 trials stipulate that you must have exhausted all standard of care options. I have not and this has never been a roadblock to participating in a trial - even when it was in the criteria.

It was a conscience decision on my part to keep my last two standard of care options in my back pocket for as long as possible. I feel that was the right decision for me. It gives me something to fall back on for, hopefully, a few months when I have exhausted all other avenues.

I have also tried to participate in trials with a gynaecological focus. ARC101 is my last trial in that area then I will have to move to Phase 1 solid tumour trials. All drugs started somewhere…so, you never know!! 

Of course, my hope is that I will be accepted for Elahere in the very near future 🤞.

@lbarr72

Thanks 🥰. 

@GloHo I'm so sorry this trial didn't work however we are all so appreciative of you continuing sharing of your experience and the information behind it all. 

#Clinicaltrialsandresearch

@Alwayslearning

Thanks so much for your continued support. My mind really is still swirling…but I heard from the trial nurse and we had a good little conversation. I am going to post another little (I hope) blurb about that.😁

CX-5461

Phase 1 study to find the right dose of CX-5461 and to look at what effects CX-5461 have in patients with solid tumours with BRCA2 and/or PARB2 mutations

Post-Trial Follow up

So, here we are at my one-month post-trial follow up.

I have not had any new symptoms from this drug and I have begun taking liberties with getting some sun (I am still careful, but gosh it feels so good!!).

I have noted something related to my CA125 counts from pre-trial to post-trial. I am going to be sharing this information with the lead oncologist on my team and it is my hope that she will pass on my post-trial patient feedback to the sponsor.

Throughout the trial, my CA125 was increasing. From pre-trial to trial end, my CA125 had increased by 8700. A significant increase for sure!

My 8-week CT scan showed definitive progress in the 20% range. 

Based solely on the CT, the decision was made to discontinue the trial. Given the above information, I totally agreed.

However, since I was removed from the trial and not having received any other treatment, I have seen more promising CA125 results. First an increase of 900 (good compared to what I was seeing in-trial), then an increase by 1650 (still better than what I was seeing in trial), and then I had a decrease of 1500!

Needless to say, I am quite disappointed that the trial was discontinued for me when these results show there may have been potential for this drug. 

I recall reading an article once where the author pondered if Drs were discontinuing new treatments too quickly. Hmmmm 🤔?

@Tanja

Believe me… I am not done with my team in relation to this issue. It will continue to be a topic that I will keep bringing up.

Because I have been at this hospital for so many different things, I keep getting different surveys to answer and I use those opportunities to voice my concerns.

I also contacted the Clinical Trials Research Unit and was given a personal one-on-one with a staff member in the unit. One of the things they are tasked with is making the patient experience better. That was a very good interview. They listened. 

@GloHo I'm guessing once the 'drug' part of the trial is no longer being administered it ends however it's certainly a curiosity as to whether they follow anyone for a short period of time who discontinued the study, just for research purposes e.g., what did you experience 15 days post end, 30 days post end, 45 days? Even that information might be interesting. I am however NOT a scientist and perhaps that's really not helpful information.

Thanks as always for sharing.

#Clinicaltrialsandresearch

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@Alwayslearning

Good question and something I've never written about.

The first trial I participated in, in 2024, just stopped following me. Each trial has a post-trial follow up schedule. It's usually a couple of phone calls and then they just follow my journey…blood work, biopsy results, change in care/trials…they have access to everything that is going on with me and they track it for a certain amount of time. They cannot apply new results to their data because it's not related to their drug. I hate to say it but I believe these trials look more at survival rates post-trial? Not sure.

Also, since I am part of the BIODIVA study, and have agreed to provide blood, fluids, etc., throughout my journey, my recent change to another trial brought about 10 vials from BIODIVA for blood collection 💉. So, this study is different in that it continues to gather my bodily fluids at key points in my journey and continues to enhance my profile. This does raise a couple of questions that I'll have to ask my BIODIVA coordinator about. That is…do they run the same tests on this new blood collection and will my Dr (or I) receive the results? Hmmmm🤔. In any case, it's nice to see and be part of research in motion 😁.

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@GloHo that is interesting indeed. Also, ten vials is A LOT! I remember my first visit to PMH in February, 2024 they took 11. I didn't think I had that much blood in me. 

Thank you for continuing to share all of this information. It's so informative. Also, thank you for continuing to participate (I'm very hopeful this one is gonna give you good results) and for being so open with your information. It will be extremely helpful for others as we go through our journeys.

#Clinicaltrialsandresearch

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