Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
Condition: Solid Tumors; Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 1

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%.
    

Detailed description: 
      This is a Phase I dose escalation strategy according to the method described by CRML
      O'Quigley and Shen [O'Quigley et al. Biometrics 1996] and commonly used in phase I trials in
      oncology.

      Six levels of doses are initially defined: 600 mg, 1200 mg, 1800 mg, 2200 mg, 2600 mg, 3000
      mg.

      The maximum potential dose-limiting toxicities allowed is 25%.

      Dose limiting toxicities 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.
    

Intervention name(s): Efavirenz 600mg; Efavirenz 1200 mg; Efavirenz 1800 mg; Efavirenz 2200 mg
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Efavirenz 600 mg (oral daily intake); Efavirenz 1200mg (oral daily intake); Efavirenz 1800mg (oral daily intake); Efavirenz 2200mg (oral daily intake)
Intervention MeSH terms: Efavirenz
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Solid tumors (other than pancreas)