Avelumab in Subjects With Merkel Cell Carcinoma

Phase 1

• Conditions: Merkel Cell Carcinoma; MedDRA version: 21.1Level: LLTClassification code 10064025Term: Merkel cell carcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000445-79-DE
• Lead Sponsor: Merck KGaA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-10-22
• Last Update Posted: 6 October 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Signed written informed consent
• Age 18 years and above
• Histologically proven MCC as defined in the protocol
• For Part A - Progressive disease after receiving 1 line of chemotherapy
for metastatic MCC
• For Part B – Subjects must not have received any prior systemic
treatment for metastatic MCC. Prior chemotherapy treatment in the
adjuvant setting (no clinically detectable disease; no metastatic disease)
is allowable if the end of treatment occurred at least 6 months prior to
study start)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0
to 1
• Estimated life expectancy of more than 12 weeks
• Disease must be measurable with at least 1 uni-dimensional
measurable lesion by RECIST Version 1.1 (including skin lesions)
• Adequate haematological and hepatic function.
• Adequate renal function as per protocol definition
• Fresh Biopsy or Archival Tumor Tissue (as per protocol definition for
Part A and Part B)
• Highly effective contraception for both male and female subjects as per
protocol definition if the risk of conception exists.
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 51
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 149

Exclusion Criteria

1.Participation in another interventional clinical trial within the past 30 days (participation in observational studies is permitted)
2. Concurrent treatment with a nonpermitted drug
3. Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anticytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody; for Part B, the Investigator must consult with the Medical Monitor and consider other co regulatory targets such as 4-1BB
4. Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy, or radiotherapy administered on non-target superficial lesions], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the investigational agent
5. Major surgery for any reason, except diagnostic biopsy, within 4 weeks and/or if the subject has not fully recovered from the surgery within 4 weeks
6. Concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of trial treatment. Short-term administration of systemic steroids (that is, for allergic reactions or the management of irAEs) is allowed while on study. Note:
Subjects receiving bisphosphonate or denosumab are eligible. Also,
subjects requiring hormone replacement with corticosteroids for adrenal
insufficiency are eligible if the steroids are administered only for the
purpose of hormonal replacement and at doses = 10 mg or equivalent
prednisone per day.
7. Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy
8. Previous malignant disease (other than MCC) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
9. Prior organ transplantation, including allogeneic stem-cell transplantation
10. For Part A, Known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS) or any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection. For Part B, known history of testing positive for HIV or known AIDS in consultation with the Medical Monitor or HBV or HCV
infection at screening (positive HBV surface antigen or HCV RNA if anti-
HCV antibody screening test positive)
11. Active or history of any autoimmune disease (except for subjects with vitiligo) or immunodeficiencies that required treatment with systemic immunosuppressive drugs
12. Known severe hypersensitivity reactions to monoclonal antibodies (Grade = 3 NCI-CTCAE v 4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partly controlled asthma)
13. Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v 4.0; however, sensory neuropathy Grade = 2 is acceptable
14. Pregnancy or lactation
15. Known alcohol or drug abuse
16. Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident / stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to

Study & Design

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