Phase 1
N=25
Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
Solid Tumors · Non-Hodgkin's Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT01878890 ↗Enrolled (actual)
25
Serious AEs
56.0%
Results posted
Jan 2021
Primary outcome: Primary: Maximum Tolerated Dose (MTD) of Efavirenz — 1200 mg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Efavirenz 600mg (Drug); Efavirenz 1200 mg (Drug); Efavirenz 1800 mg (Drug); Efavirenz 2200 mg (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Institut Bergonié
- Primary completion
- Sep 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Efavirenz |
1200 | — |
| PRIMARY Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) |
0; 3; 1; 3 | — |
| SECONDARY 12-week Objective Response Rate |
— | — |
| SECONDARY 12-week Non-progression Rate |
— | — |
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%.
Eligibility Criteria
Inclusion Criteria
- Patients with solid tumors (except pancreatic cancer) or non-Hodgkin lymphoma
- Metastatic disease or locally advanced inoperable tumor, not accessible to standard therapy.
- Male or female ≥ 18 years and 1 according to the criteria CTCAE V4.0, due to prior cancer therapy.
- Recurrent diarrhea which can interfere with drug absorption capacity.
- Patient included in another biomedical research on a drug within 30 days of inclusion.
- Patient who previously participated in this study.
- Patient, who for reasons psychological, psychiatric, social, family or geographical could not be treated or monitored regularly by the criteria of the study, patients deprived of liberty or under tutorship.
Data sourced from ClinicalTrials.gov (NCT01878890). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.