Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
Status:
Completed
Trial end date:
2016-12-31
Target enrollment:
Participant gender:
Summary
Hypothesis: encouraging results of phase II study FAVE in the treatment of hormonal resistant
prostate cancer lead us to continue clinical development of efavirenz. Furthermore, all
available pre-clinical and clinical data lead us to conduct a Phase 1 study with efavirenz.
Objective of this Phase I is to test doses above 600 mg / day in patients with cancer in
order to determine the maximum tolerated dose to improve therapeutic effect.
This study is a single center Phase I trial, conduct with dose escalation scheme of efavirenz
by continual reassessment method likehood approach (CRML) on solid tumours (except pancreatic
cancer) and non-Hodgkin lymphoma (NHL).
Main objective is to determine the safety profile, and particularly the maximum tolerated
dose of efavirenz for the treatment of patients with solid tumors (except pancreatic cancer)
or NHL in therapeutic failure.
Secondary objectives are:
- Evaluate efavirenz pharmacokinetics at 2, 4 and 12 weeks;
- Evaluate objective response at 12 weeks;
- Evaluate progression free survival at 6 months;
- Assess biological progression-free survival at 6 months (prostate tumours only).
Primary Endpoint
Safety will be evaluated according to the toxicity scale NCI-CTCAE v4.0. Dose limiting
toxicities will be collected during the first 28 days (+ / - 7 days) after first dose of
Efavirenz and will be defined as follows:
- Any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia,
nausea and vomiting, regardless of grade),
- Any drug-related toxicity, regardless of grade, who led a treatment delay> 14 days,
- Score ≥ 19 HAD during treatment. Secondary Criteria
- Solid tumors: response and progression defined by RECIST v1.1 [Eisenhauer EA et al. EJC
2009).
- Non-Hodgkin lymphomas: Response and progression defined according to Cheson criteria
[Cheson BD et al. JCO 1999]
- Biological progression (particular case of prostate tumors): defined according to Scher
[Scher HI et al. JCO 2008] Statistical Considerations This is a Phase I dose escalation
strategy using the method CRML, described by O'Quigley and Shen [O'Quigley et al.
Biometrics 1996] and commonly used in Phase I trials in oncology.
- Maximum number of eligible and evaluable subjects is 30.
- Six dose levels are initially defined: 600 mg, 1200 mg, 1800 mg, 2200 mg, 2600 mg, 3000
mg.
- The risk of dose limiting toxicities maximum allowed is 25%.