Deciding on a clinical trial
Summary
I was eligible for the UCSF EVEREST (Everolimus/Affinitor) Clinical Trial within 84 days of my operation. I declined participation since the ESPN trial indicated that Everolimus is not effective against stage 4 papillary cancer, and I did not want to be a confound for a any (potential) upcoming clinical trials.
Discussion
So. How does one decide whether or not to participate in a clinical Trial? My approach was to ask 13 people and I figured that I’d go with the majority. Here is the question I asked.
“Should Bill participate in the EVEREST (Everolimus) Trial?”
The tally is below. Three said yes, five said no and five said I needed to decide myself. The ESPN clinical trial results were not yet reported, so I pestered the PI via email twice and used his answer to support my decision.
- Yes- Gastro + Urologist
- Yes – Stanford Oncologist – “If you are eligible always a good idea to partake on trials”
- Yes – Sutter Primary Care Physician – “Minimal Downside”
- No – M.D. Anderson Oncologist (ran ESPN trial) – “I do not recommend any adjuvant trial w/ mTOR inhibitors or VEGF targeted agents for papillary RCC. There will be trials w/ immune checkpoint agents in the near future but not soon enough to enroll on.”
- No – Los Gatos Hematologist
- No – Waco Oncologist
- No – Danish Researcher
- No – German General Practitioner (not yet translated)
- Bill must decide – Parisian Oncologist
- Bill must decide – HK Internist
- Bill must decide – Radiation Oncologist
- Bill must decide – UCSF Primary Care Physician
- Bill must decide – MD Anderson Pharmacist
- – JHH Hospitalist
Everest Details: Everolimus, the drug used in the Everest trial, has many side effects, and may damage my remaining kidney, which is already impaired (Creatinine level, a proxy for my kidney’s ability to function, is at 1.56. Normal is 1.0 eGFR is 46. Normal is >60.). Here is the NP’s response to this question:
- What dosage would I be taking?The dose for the non metastatic patient, participating on the EVEREST clinical trial, is 10 mg daily (100% of patients participating in the trial have only 1 kidney)
- What is the usual dosage for stage 4 RCC and for a kidney transplant?The dose of everolimus for treatment of metastatic kidney cancer (stage 4) is also 10 mg daily (probably well over 90-95% of these patients have only 1 kidney) The dose for kidney transplant is a completely different ball of wax and is not comparable to kidney cancer. It is given to patients at risk for rejection of their transplanted organ. I am less familiar with this usage but from what I understand, the dose starts at 0.75 mg and is adjusted daily based on blood concentration levels. This dosage would not be adequate to exert an anti-tumor effect.
- How would you determine if renal failure is occuring?Renal failure in the setting of everolimus is uncommon, occurring in only 3% of patients. Elevations in serum creatinine levels have been observed in 19-50% of patients but this is not the same thing as renal failure. We monitor for elevations in one’s creatinine by following a monthly creatinine blood test along with other monthly lab tests.I understand your concern and desire to take care of your one remaining kidney but significant kidney toxicity from everolimus is not really that common. The message below mentions possibly starting at a lower dose than standard. The trial does not allow this. When it comes to cancer drugs, a certain level of drug needs to be present to exert an anti-tumor effect. If certain toxicities are observed, a small dose adjustment may be indicated but this may also sacrifice some of the anti-tumor effect.
Bibliography
- 20140530 ESPN – Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (The ESPN Trial): A multicenter randomized phase 2 trial “E(verolimus) cannot be recommended as 1L option in nccRCC.” Nizar Tannir – “I do not recommend any adjuvant trial w/ mTOR inhibitors or VEGF targeted agents for papillary RCC. There will be trials w/ immune checkpoint agents in the near future but not soon enough to enroll on.” {BP: Read Somewhere that ESPN sample was too small to draw this conclusion, but also see ASPEN }
- Everest
- pdf Everolimus in the Treatment of Renal Cell Carcinoma and Neuroendocrine Tumors
- pdf Everolimus or Affinitor in the adjuvant setting
- pdf A Phase Ib Study of Combined VEGFR and mTOR Inhibition With Vatalanib and Everolimus in Patients With Advanced Renal Cell Carcinoma
- pdf Long lasting response to second-line everolimus in kidney cancer
- pdf Impact of everolimus blood concentration on its anti‐cancer activity in patients with metastatic renal cell carcinoma
- pdf GOAL: An inverse toxicity-related algorithm for daily clinical practice decision making in advanced kidney cancer
- pdf Everolimus