Increasing Clinical Trials in Cholangiocarcinoma – Dr. Zhu, Dr. Borad,

Katrina….great input. Prior to the ABC-2 study, there was no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer.

This clinical trial proved that the gemcitabine/cisplatin combination increases life expectancy by approximately 1.1 years. Note: Intrahepatic patients faired not quite as well.
https://clinicaltrials.gov/show/NCT00262769

You, – similar to the majority of resected patients – received gem/cis in an adjuvant setting (post surgery) and appeared to have minor, positive response. The reality is, we don’t know whether resected patients benefit from chemotherapy.

This question will be answered with 2 conducted and completed studies. We are awaiting data outcome of the BilCap study:
Xeloda or observation only:
https://clinicaltrials.gov/ct2/show/NCT00363584

and the Prodige12 study:
https://clinicaltrials.gov/ct2/show/NCT01313377

So happy to know that the second surgery removed the cancerous lymph node.

Hugs,
Marion

You are most welcome, dear Gavin.

In regards to effectiveness (efficacy) shown early in the study phase II or Phase III the sponsor (pharmaceutical company) is eligible to request ” Breakthrough” designation.
This accelerated approval request must be accompanied by “preliminary” evidence indicating that the drug demonstrated substantial improvement over existing therapies
FDA approval then assures quick application of drug to general patient population.

What are clinically significant endpoints?
1. Response to drug – usually the primary endpoint in phase II trials

CR (Complete Response) = no “detectable” tumor is evident (also called “NED” – no evidence of disease -) Potentially the treatment was curative.
Note: Although there is no evidence of tumor(s) patient may not be cured. CT or other scans have limitations in that it residual tumor may be too small to be visible.

Partial Response to drug (PR) – at least a 50% decrease in the total tumor volume.

With evidence of some residual disease, a partial response is not curative because: a significant amount of tumor remains.
Note: some patients show evidence of remaining tumor however; they may achieve a complete response with continued treatment. Also visible, residual “tumor” may relate to “dead” tumor or “scar” tissue.

In adjuvant setting (following “potentially curative surgery)
Disease Free Survival or Progression Free Survival: generally used as endpoints In Phase III, randomized trials (people chosen at random):

Progression Free Survival: patient is alive and free of any significant cancer increase
Disease Free Survival is connected to Progression Free Survival and is used as endpoint of adjuvant therapy, clinical research study (trial) i.e. measure of recurrence of disease following surgery to remove all visible cancer. These types of trials need comparisons i.e. randomization.

Hugs
Marion

Marilyn,

Thank you, thank you for the great explantion…..simplistic or not…..that’s what I needed. I didn’t realize some of the “studies” I’d seen were just academic studies…but that explains everything. Now to be patient. But, I’m an impatient, patient. It’s kind of “after the fact” for me, having already done the adjuvant chemo, but I’d still like to know. ))))

Julie T.

Marilyn, Thanks for going over the study info. I didn’t know if it was like a trial for a drug…..once they discover a drug has fantastic response, (don’t know how often this actually happens) the drug is offered to all parties involved (and similarly, when a drug isn’t working as expected…or even having opposite results (as I believe some drugs in heart studies….and estrogen?….is that the one??)…..they pull the drug before the projected end). I thought maybe that if the saw a pretty dramatic result, it seems ethically, they should need to inform the public and medical community. When I saw 8 years on there…..I was pretty discouraged. That is 8 more years of people not knowing based on any research whether to do adjuvant chemo or not.

That said….I “thought” there HAD been some studies….showing that adjuvant chemo does have some good effect….in particular where there are positive margins and positve lymph nodes, but not where everything “looks” good. Am I imagining that? I thought for sure I had read that in some of the study posts that you or Gavin had posted on the foundation website. If that was the case….why is Germany doing this big study? Is it just for the much larger size of the study…and thus a better chance of being statistically more accurate?

Julie T.

Thanks Marion. I watched most of the video, but stopped when I couldn’t hear what was being said. Even so, I had gotten lost pretty fast, so I really appreciated your post with the recap of some of the info that was discussed.

Do I understand correctly that the results of the German trial to see if Gem/Cis used as adjuvant therapy following a resection will not be available until 2022? Do they do preliminary reports on what they see happening?

Julie T.

Thanks, Gavin.
This presentation encompassed many important issues – it’s worth the watch – I will try to answer questions you may have.

We are awaiting the data from several clinical trials which may potentially change treatments of Cholangiocarcinoma patients.

Although the majority of physicians recommend adjuvant (post resection) chemotherapy, the outcome of the (3) below mentioned clinical research studies will prove/disprove the validity of this approach.

UK: https://clinicaltrials.gov/ct2/show/NCT00363584
Do extrahepatic (hilar and distal) resected CCA patients benefit from adjuvant therapy with Capecitabine (Xeloda?

France: https://clinicaltrials.gov/ct2/show/NCT01313377
Do extrahepatic (hilar and distal) resected CCA patients benefit from adjuvant GEMOX treatment?

Germany: https://clinicaltrials.gov/ct2/show/NCT02170090
Do CCA (intrahepatic, hilar, distal) resected patients benefit from adjuvant GEM/CIS treatment?

The below study is comparing progression free survival of extrahepatic (hilar, distal) CCA with advanced or metastatic disease, who have been treated with Gem/Cis as first line of treatment but now have progressed.
Korea: https://clinicaltrials.gov/ct2/show/NCT01470443
Is XELOX as effective as GEMOX?

The ABC-6 study
UK: https://clinicaltrials.gov/ct2/show/NCT01926236
CCA patients (intrahepatic, distal, hilar) non metastatic, but locally advanced, who are fully active, able to carry on all pre-disease performance without restriction or may be restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. One arm (group) of participants will receive monthly clinical review and active symptom control as needed, including biliary drainage, antibiotics, analgesia, steroids, anti-emetics, other palliative treatment for symptom control, palliative radiotherapy, blood transfusion.
The other control group will receive FOLFOX.

USA https://clinicaltrials.gov/ct2/show/NCT02200042
Intrahepatic, non-resectable, localized progressed (non-metastatic) CCA patients are divided in 2 groups:
Group A: will receive Gem/Cis
Group B: will receive Gem/Cis plus radiation. With or Without Radiation Therapy in Treating Patients With Localized Liver Cancer That Cannot Be Removed By Surgery

Hugs,
Marion