Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.

NCT01878890 | Completed Phase 1 Results

• 1 other identifier: IB2011-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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%.

Conditions

Solid Tumors; Non-Hodgkin's Lymphoma

Keywords

Solid tumors (other than pancreas)

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Efavirenz

  MTD was determined by testing increasing doses up to 3000 mg (oral daily intake). The dose escalation scheme is the continual reassessment method likehood approach (CRML) described by O'Quigley and Shen \[O'Quigley et al. Biometrics 1996\]. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 25% of participants. A DLT was 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, a score ≥ 19 for the Hospital Anxiety And Depression Scale (HAD) during treatment.

  Up to 28 days for each dosing cohort

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  A DLT was 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, a score ≥ 19 for the Hospital Anxiety And Depression Scale (HAD) during treatment.

  Up to 28 days for each dosing cohort

Secondary Outcomes (2)

• 12-week Objective Response Rate

  up to 3 months after first adminitration of Efavirenz

• 12-week Non-progression Rate

  Evaluated up to 3 months after first administration of Efavirenz

Study Arms (4)

Efavirenz: 600 mg

EXPERIMENTAL

Cohort 1 : Participants received 600 mg of Efavirenz (oral / once a day), until progression or toxicity.

Drug: Efavirenz 600mg

Efavirenz: 1200 mg

EXPERIMENTAL

Cohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity.

Drug: Efavirenz 1200 mg

Efavirenz: 1800 mg

EXPERIMENTAL

Cohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity.

Drug: Efavirenz 1800 mg

Efavirenz: 2200 mg

EXPERIMENTAL

Cohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity.

Drug: Efavirenz 2200 mg

Interventions

Efavirenz 600mg DRUG

Efavirenz 600 mg (oral daily intake)

Efavirenz: 600 mg

Efavirenz 1200 mg DRUG

Efavirenz 1200mg (oral daily intake)

Efavirenz: 1200 mg

Efavirenz 1800 mg DRUG

Efavirenz 1800mg (oral daily intake)

Efavirenz: 1800 mg

Efavirenz 2200 mg DRUG

Efavirenz 2200mg (oral daily intake)

Efavirenz: 2200 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \<80 years.
• Tumor assessable by RECIST v1.1, Scher Cheson 2008 or 99.
• At least 28 days after completion of prior treatment (radiotherapy, systemic chemotherapy or major surgery).
• Patient who recovered from any prior toxicity ≤ grade 1.
• Neutrophils ≥ 1500/mm3, Platelets ≥ 100 000/mm3.
• Total bilirubin and serum creatinine within normal limits (≤ 1.5 ULN), creatinine clearance ≥ 40 ml / min.
• AST / ALT ≤ 1.5 ULN (≤ 5 ULN if liver metastasis).
• Normal thyroid function.
• Normal coagulation: TP ≥ 70%.
• Life expectancy upper than 3 months.
• HAD score \<13.
• Effective contraception for the duration of treatment (for both sexes in childbearing or reproductive age): mechanic contraception method should always be used in combination with other contraceptive methods (eg, oral or other hormonal contraceptives). Because of long half-life of efavirenz, it is recommended to use adequate contraceptive measures for 12 weeks after stopping treatment with efavirenz.
• Informed consent signed and dated by the patient or his legal representative before the establishment of any specific procedure to the study.

You may not qualify if:

• Patient with pancreatic cancer.
• Presence of active or symptomatic cerebral localization (known).
• History of another cancer except:
• cancer occurred more than five years and considered in complete remission
• in situ cervix carcinomas,
• cutaneous basal cell carcinomas.
• Current major depressive state (screening by HAD scale total score ≥ 13).
• Patients with history of depressive disorders, suicide attempts, addiction or other psychiatric disorders.
• Concomitant use of terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, alkaloids of ergot, voriconazole, mixing St. John's Wort.
• Patients treated with anti-vitamin K. Treatment with low molecular weight heparin are allowed.
• Known efavirenz hypersensitivity or to any of its excipients.
• Severe renal impairment.
• Severe hepatic impairment.
• Yellow fever vaccine (yellow fever).
• Pregnant or lactating.

Sponsors & Collaborators

• Institut Bergonié: lead

Study Sites (1)

Institut Bergonié

Bordeaux, 33076, France

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

efavirenz

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr Guilhem Roubaud
• Organization: Institut Bergonié

g.roubaud@bordeaux.unicancer.fr

33 5 56 33 33 33

Study Officials

• Guilhem Roubaud, MD

  Institut Bergonié

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2012
• First Posted: June 17, 2013
• Study Start: September 5, 2011
• Primary Completion: September 16, 2014
• Study Completion: December 31, 2016
• Last Updated: January 27, 2021
• Results First Posted: January 27, 2021

Record last verified: 2021-01

Locations

FR (1)