Adjuvant Therapy of Completely Resected Merkel Cell Carcinoma With Immune Checkpoint Blocking Antibodies vs Observation

• Status: Active, not recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective:

To estimate the efficacy of adjuvant nivolumab monotherapy in completely resected Merkel cell carcinoma (MCC) patients; i.e. the primary endpoint is disease-free survival (DFS) in arm A at 12 months, defined as the number of patients alive and free of disease at 12 months after randomization compared to DFS in arm B.

Secondary Objective:

To assess safety and additional efficacy parameters of the nivolumab treatment in MCC, as well as to characterize potential biomarkers; secondary endpoints are:

(i) Adverse events according to CTCAE, Version 4.0 criteria, that are definitely, probably, or possibly related to the administration of nivolumab

(ii) Overall survival rate at 12 months, defined as the number of patients surviving at 12 months after randomization divided by the total number of patients randomized.

(iii) DFS rate at 12 months, defined as the number of patients alive and free of disease at 12 months after randomization divided by the total number of patients randomized

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Prof. Dr. med. Dirk Schadendorf
• Collaborator: Bristol-Myers Squibb
• Treatments: Antibodies, Monoclonal; Nivolumab

Criteria

Inclusion Criteria:

1. The patient is willing and able to give written informed consent.

2. Central histological confirmation of diagnosis of Merkel cell carcinoma (MCC).

3. All MCC manifestations have been completely resected by surgery within 12 weeks before enrolment.

4. No currently present metastases (as confirmed by standard imaging studies (e.g. suggested by S2k guidelines)).

5. No previous systemic therapy for MCC.

6. Required values for initial laboratory tests:

• WBC ≥ 2000/uL

• ANC ≥ 1000/uL

• Platelets ≥ 75 x 103/uL

• Hemoglobin ≥ 8 g/dL (≥ 80 g/L)

• Creatinine ≤ 2.0 x ULN

• AST/ALT ≤ 2.5 x ULN

• Total Bilirubin ≤ 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)

7. ECOG performance status 0 or 1.

8. No active or chronic infection with HIV, Hepatitis B (HBV) or C (HCV).

9. Men and women, ≥ 18 years of age.

10. Women of childbearing potential (WOCBP) must be using an adequate method of contraception (Pearl-Index < 1) to avoid pregnancy during treatment phase and for additional 5 months after the last dose of nivolumab, in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of nivolumab.

11. Men of fathering potential must be using an adequate method of contraception to avoid conception and for 7 months after the last dose of nivolumab in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria:

1. Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease requiring systemic steroids (e.g., rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus, autoimmune vasculitis); autoimmune motor neuropathy.

2. Other serious illnesses, e.g., serious infections requiring i.v. antibiotics.

3. The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immune deficient condition.

4. Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of nivolumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea.

5. Any non-oncology vaccine therapy for up to 1 month before or after any dose of nivolumab.

6. A history of prior or current treatment with a T cell potentiating agent (e.g. IL-2, interferon, anti-CTLA-4, anti-CD137, anti-PD1, anti-PD-L1, or anti-OX40 antibody).

7. Chronic use of immunosuppressive agents or systemic corticosteroids.

8. Women of childbearing potential (WOCBP), defined above in Section 5.1, who:

• are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for additional 5 months after the last dose of investigational product

• have a positive pregnancy test at baseline

• are pregnant or breastfeeding.

9. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.

10. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.

11. Men of reproductive potential unwilling to use an adequate method to avoid pregnancy for additional 7 months after the last dose of investigational product.

12. Use of any investigational or non-registered product (drug or vaccine) other than the study treatment.