Prospective randomized trial of an adjuvant therapy of completely resected Merkel Cell Carcinoma (MCC) with immune checkpoint blocking antibodies (Nivolumab, Opdivo®; Ipilimumab, Yervoy®) versus observatio

Phase 2

• Conditions: Merkel cell carcinoom (MCC) - neuroendocrine carcinoma of the skin; 10029112; 10040900

• Registration Number: NL-OMON50102
• Lead Sponsor: niversity Hospital Essen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 30

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 of 0 or 1.
8. No active or chronic infection with HIV, Hepatitis B or C.
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 during treatment phase and for additional 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 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 during treatment phase and 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 during treatment phase and 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective is of the study is to estimate the efficacy of adjuvant<br /><br>nivolumab monotherapy in completely resected MCC patients; i.e. the primary<br /><br>endpoint is Disease-free survival (DFS) in arm A at 12 months, defined as the<br /><br>number of patients alive and free of disease at 12 months after randomization<br /><br>compared to DFS in arm B.</p><br>