CT scan series part 10 - Clinical Trial CT scan Context

[ThreeWs]

CT scan series part 10 - Clinical Trial CT scan Context

There is solid rationale for CT-scanning in a Clinical Trial setting that cannot be avoided but is it adequate or overkill? Who decides?

There are so many newer drugs that promise better efficacy with less toxicity that it is hard to keep up with them. All these drugs will require Clinical Trials that must produce evidence of efficacy and safety. Ibrutinib and Idelalisib are two drugs that illustrate the difficulty for obtaining that evidence. These two drugs initially cause an increase of cancer cells in the peripheral blood, unlike standard chemo and mAbs that show an immediate decrease as the cells are killed off. Many lymphnodes are not visually observed or felt by palpation but can be used as evidence of efficacy if objectively measured to prove reduction of the total tumor burden, even while ALC (Absolute Lymphocyte Count) is on the rise. Is this objective measurement of lymphnodes via CT scanning necessary to the drug developer in order to convince the FDA of a drug's efficacy which will lead to approval?

Just yesterday I made contact with an NCI researcher who provided a number of insights. I asked who is responsible for setting the criteria that involves CT scans for the evidence of drug efficacy and safety that will be required for FDA approval? He explained that the gold standard for drug approval is OS (Overall Survival) and in the absence of that there are surrogate endpoints. I remember Dr. Byrd musing on the dilemma of quantifying the “feeling Great” reaction of so many Ibrutinib patients soon after taking the drug in the early Trials. Is patient subjective reaction regarding quality of life a valid endpoint?

The TKIs (Ibrutinib and Idelalisib) have made endpoint evaluation an important goal for FDA approval and may be a major factor behind frequent CT use. I am still working on who is setting the CT use agenda and what is really necessary as opposed to what is being done. Questions I have not received adequate answers for revolves around who decides how many scans a Clinical Trial Lab-Rat will get and is there a patient advocate perspective in the decision process? Even if frequent scans are deemed necessary, is anyone setting out guidelines for institutions conducting Clinical Trials assuring that Lab-Rats like you and me are getting those scans on the lowest radiation dose machines?

A recent personal story illustrating my concerns occurred during the recent Needham, MA LRF Conference where one of the two Dana Farber Oncologists giving a formal presentation gave the now familiar nudge to the audience on participating in Clinical Trials and the also familiar warning off of inappropriate CT scanning. Both subjects I had planned to ask questions about. At questions from the audience, I emphasized the doctor's push for Clinical Trial participation by describing my experience with PCI-32765 (Ibrutinib) and finished up by saying I wished to pick up on an issue related to unnecessary CT scanning in the Clinical Trial context. I said I had not been treated at Dana Farber and since I assumed that he was involved in Clinical Trials, what was Dana Farber, as an institution or he as an investigator doing to minimize ionizing radiation to Clinical Trial patients and what could he tell the audience about CT machines used at Dana Farber that used low dose technology?

His reaction was to look down at his watch in an uncomfortably long pause and finally he blurted out “I don't know what machines are used but if you have a problem with radiation exposure you should take it up with the pharmaceutical company – next question.”

I don't know about you but at that point I no longer had a problem with just radiation exposure but a problem with who is looking out for the patients who are being asked to endure frequent scanning. For the record, I volunteered for the NIH Natural History Study in which I knew I would be scanned and at a time where I had a record of scan refusal by local oncologist recommendation. I believe in the progress of advancing medical breakthroughs by Trial participation but I want to know somebody has our back on safety issues. That Dana Farber Doc did not inspire confidence that Clinical Trial patients were indeed anything more than Lab-Rats.

WWW

[lankisterguy Volunteer]

As I posted on another site, WWW's long treatise on this subject sparked a conversation with my clinical trial doc, where I learned that I could refuse a reasonable number of the 6 CT Scans scheduled on my trial and not be forced off the trial. Also, the trial protocol included a second scan of the head & neck, which seems superfluous. So I am planning to take 2 trips through the scanner each year, instead of the 12 that the protocol specifies.

Thanks Wayne for leading the quiet, polite revolt of the lab rats!

[Mikey47 in reply to lankisterguy]

Hi Lenkeck,

I have 9 scans scheduled (RESONATE-2). I have asked for MRI scans instead of the CTs but it is up to the trial team. My consultant will put my request to them.

My scans are neck to pelvis and are reckoned to be 10mSvts each. I have also had a PET scan which may be even more. I have just had a suspected Basal Cell Carcinoma excised from my face. If I can't swap the scans I'm prepared to leave the trial if necessary.

Which trial are you on?

[ThreeWs in reply to Mikey47]

Hi Mikey47

I had concerns over not achieving the proper balance between what is properly perceived as currently a too casual use of CTs by general Oncs and excessive scanning in the Clinical Trial context as opposed to scaring the hell out of folks causing them to forego benefits of Clinical Trial drugs.

Do consider how well the Trial is working for you before leaving it in spite of the scanning issue. Your bringing the issue to the attention of your treating Doctor and Trial Team will help change the culture of CT use to benefit all patients.

Remember that change doesn't happen top down. Lab-Rats Rule!

WWW

[lankisterguy Volunteer]

I am on Gilead 117 trial- Idelalisib (extension of Gilead 116 that had 8 Ritxan infusions + placebo or active Idelalisib )

When the 116 was completed and reported last year, I was one of the successes that achieved CR. But the 117 extension restarted the frequent clinic visits and CT Scans as if I had progressed to needing treatment.

Dr. Furman my trial doctor agrees that 6 double CT Scans are excessive for somone in CR. If my blood counts or symptoms indicate progression then the doctor may alter his position.

If you want to follow this approach, getting aligned with your trial doctor is likely the most important first step.

Idelalisib is keeping me in CR and I will do whatever I must to assure my supply of that drug. If I can stay in my trial and reduce the risk from radiation and secondary cancers I will sieze every opportunity I can.

[ThreeWs in reply to lankisterguy]

Hi Len,

This is exactly the type of dialogue that I had hoped to promote and your efforts will hopefully be reflected in other patient experiences for reduced radiation exposure.

WWW