A non-comparative randomized phase II study evaluating atezolizumab in combination with docetaxel, cisplatin, and 5-fluorouracil for the treatment of metastatic or unresectable locally advanced squamous cell anal carcinoma

Phase 1

• Conditions: Metastatic or unresectable locally advanced squamous anal carcinoma; MedDRA version: 20.0Level: LLTClassification code 10002141Term: Anal carcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003185-27-FR
• Lead Sponsor: GERCOR

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-19
• Last Update Posted: 23 July 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

1. Male or female, aged =18 years,
2. Performance status Eastern Cooperative Oncology Group World Health Organization (ECOG-WHO) =1,
3. Histologically proven and unresectable locally advanced recurrent or metastatic squamous cell anal carcinoma,
4. Presence of a target lesion on CT-scan assessed by RECIST v1.1 criteria,
5. Patient eligible to the mDCF regimen,
6. CT scan performed within 28 days prior inclusion,
7. PET scan performed within 28 days prior inclusion,
8. Signed and dated informed consent,
9. Patient affiliated to or beneficiary of French social security system,
10. Ability to comply with the study protocol, in the Investigator’s judgment,
11. Life expectancy >=6 months,
12. Adequate hematologic and end-organ function.
NB: Previous concomitant chemoradiotherapy is allowed.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 66
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 33

Exclusion Criteria

1. Previously received chemotherapy for metastatic disease,
2. Previously received cisplatin except for concomitant chemoradiotherapy,
3. Previously received taxanes (paclitaxel or docetaxel) or another spindle poison (navelbine) in the treatment of SCCA,
4. Previously received anti-tumor immunotherapy (HPV vaccination is allowed),
5. Diagnosis of additional malignancy within 3 years prior to the randomization with the exception for curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer,
6. Any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study,
7. Current participation in a study of an investigational agent or in the period of exclusion,
8. Pregnancy, breast-feeding or absence/refusal of adequate contraception for fertile patients during the period of treatment and for 6 months from the last treatment administration,
9. Patient under guardianship, curatorship or under the protection of justice.
10. Inadequate organ functions: uncontrolled cardiac condition, known cardiac failure, unstable coronaropathy, respiratory failure, and Chronic Obstructive Pulmonary Disease (COPD),
11. Diabetes with vascular or neurovascular complications,
12. Preexistent peripheral neuropathy or impaired audition,
13. HIV positive with CD4 count under 400 cells/mm3 (VIH test is mandatory before inclusion),
14. Active hepatitis B or C virus (HBV or HCV) infection (chronic or acute), (Defined as having a positive HBV surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total HBV core antibody (HBcAb) test at screening, are eligible for the study.
15. Active tuberculosis,
16. Concomitant treatment with CYP3A4 inhibitor like ritonavir, indinavir, or ketoconazole, etc. Replacement by another drug before randomization, whenever is possible, is allowed,
17. Known hypersensitivity or contraindication to any of the study chemotherapy drugs (taxanes, cisplatin, 5FU),
18. Uncontrolled infection or another life-risk condition,
19. Known hearing impairment that contraindicates cisplatin administration,
20. Administration of a live (attenuated) vaccine within 28 days of planned start of study therapy of known need for this vaccine during treatment,
21. Administration of prophylactic phenytoin,
22. Inadequate laboratory values: creatinine clearance <60 ml/min, neutrophil count <1500 /mm3, platelets <100000/mm3, bilirubin 2.5 x upper limit of normal (ULN), aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 x ULN or 5 x ULN with liver metastasis.
Non-eligible to immunotherapy:
23. Any immunosuppressive therapy (i.e. corticosteroids >10mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy,
24. Active autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin) is allowed.
Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, (see Annex 7 for a more comprehensive list of autoimmune diseases and im

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified