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

This is an interventional treatment trial for Solid Tumors focused on measuring Solid tumors (other than pancreas) Read More

Inclusion Criteria :

1. Patients with solid tumors (except pancreatic cancer) or non-Hodgkin lymphoma
2. Metastatic disease or locally advanced inoperable tumor, not accessible to standard therapy.
3. Male or female ≥ 18 years and <80 years.
4. Tumor assessable by RECIST v1.1, Scher Cheson 2008 or 99.
5. At least 28 days after completion of prior treatment (radiotherapy, systemic chemotherapy or major surgery).
6. Patient who recovered from any prior toxicity ≤ grade 1.
7. WHO 0-1 in the 7 days before inclusion.
8. Neutrophils ≥ 1500/mm3, Platelets ≥ 100 000/mm3.
9. Total bilirubin and serum creatinine within normal limits (≤ 1.5 ULN), creatinine clearance ≥ 40 ml / min.
10. AST / ALT ≤ 1.5 ULN (≤ 5 ULN if liver metastasis).
11. Normal thyroid function.
12. Normal coagulation: TP ≥ 70%.
13. Life expectancy upper than 3 months.
14. HAD score <13.
15. Negative pregnancy test for women likely to be pregnant within 7 days before inclusion.
16. 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.
17. Informed consent signed and dated by the patient or his legal representative before the establishment of any specific procedure to the study.
18. Clinical examination and laboratory tests made within 7 days before enrollment and start of treatment.
19. Initial assessment and radiological CT / or MRI performed within 30 days before enrollment.
20. Patients potentially compliant with treatment and follow-up study.
21. Ability to swallow capsules or tablets.
22. Patients insured by a social security system.

Exclusion Criteria :

1. Patient with pancreatic cancer.
2. Presence of active or symptomatic cerebral localization (known).

3. History of another cancer except:

   • cancer occurred more than five years and considered in complete remission
   • in situ cervix carcinomas,
   • cutaneous basal cell carcinomas.
4. Current major depressive state (screening by HAD scale total score ≥ 13).
5. Patients with history of depressive disorders, suicide attempts, addiction or other psychiatric disorders.
6. Concomitant use of terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, alkaloids of ergot, voriconazole, mixing St. John's Wort.
7. Patients treated with anti-vitamin K. Treatment with low molecular weight heparin are allowed.
8. Known efavirenz hypersensitivity or to any of its excipients.
9. Severe renal impairment.
10. Severe hepatic impairment.
11. Yellow fever vaccine (yellow fever).
12. Pregnant or lactating.
13. Presence of toxicity> 1 according to the criteria CTCAE V4.0, due to prior cancer therapy.
14. Recurrent diarrhea which can interfere with drug absorption capacity.
15. Patient included in another biomedical research on a drug within 30 days of inclusion.
16. Patient who previously participated in this study.
17. 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.