Immunotherapy Adjuvant Trial in Patients With Stage I-III Merkel Cell Carcinoma

NCT ID: NCT04291885

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-26
• Study Completion Date: 2030-04-30

Brief Summary

The I-MAT trial is a randomised, placebo-controlled, phase II trial of adjuvant Avelumab in patients with stage I-III Merkel cell carcinoma aiming to explore the efficacy of avelumab as adjuvant immunotherapy.

Detailed Description

The I-MAT trial is a phase II, prospective, randomised, placebo-controlled, multi-institutional trial for patients with stage I-III Merkel cell carcinoma (MCC). Participants on the trial will receive either avelumab or placebo for 6 months. The primary aim of the I-MAT trial is to develop an effective, well-tolerated adjuvant immunotherapy regimen for patients with stage I-III MCC, post a range of definitive loco-regional treatment options.

Conditions

Merkel Cell Carcinoma; Merkel Cell Carcinoma, Stage I; Merkel Cell Carcinoma, Stage II; Merkel Cell Carcinoma, Stage III; Neuroendocrine Tumors; Carcinoma Neuroendocrine Skin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Avelumab

6 months of Avelumab at a dose of 800mg as a 60-minute intravenous (IV) infusion once every 2 weeks (13 doses)

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

Avelumab IV infusion

Placebo

6 months of Placebo as a 60-minute intravenous (IV) infusion once every 2 weeks (13 doses)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo IV infusion

Interventions

Avelumab

Avelumab IV infusion

Intervention Type: DRUG

Placebo

Placebo IV infusion

Intervention Type: DRUG

Other Intervention Names

anti-PD-L1; Bavencio

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed Merkel cell carcinoma (MCC) which is either:

• clinical stage I;
• pathological stage I with positive LVSI only;
• clinical or pathological stage II (including IIA and IIB);
• clinical or pathological stage III (including IIIA and IIIB).

2. Absence of distant metastatic disease on baseline 18-Fludeoxyglucose (18FDG) - Positron Emission Tomography (PET) / Computed Tomography (CT) scan.

3. 18 years of age or older.

4. Eastern Cooperative Oncology Group (ECOG) of 0 - 2.

5. Willing and able to provide written informed consent and comply with all study requirements.

6. Adequate haematological, liver and renal function as determined by the screening laboratory values outlined in the protocol obtained within 14 days prior to randomisation.

7. Agreeable to collection of archival tumour material. Where possible, the most recently acquired tumour specimen should be provided.

8. Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to the start of treatment.

Exclusion Criteria

1. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest significant risk for immune-related adverse events.

2. Prior treatment with an agent that blocks the PD-1/PD-L1 pathway.

3. Previous cancer immunotherapy, specifically interferon, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways are not permitted.

4. Prior treatment with other immune-modulating agents that was within fewer than 28 days prior to the first dose of Avelumab.

5. Active infection requiring antibiotics within 7 days of cycle 1 day 1 of study drug dose.

6. Active tuberculosis.

7. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

8. Uncontrolled infection with hepatitis B or hepatitis C virus (HBV or HCV) infection; Patients with previously successfully treated HCV, with positive anti-HCV antibody but undetectable (HCV) ribonucleic acid (RNA) levels are allowed on trial.

9. Current use of immunosuppressive medication, except for the following: a. intranasal, inhaled, topical steroids, or local steroid injection ; b. systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. steroids as premedication for hypersensitivity reactions

10. Any systemic anti-cancer treatment (chemotherapy, targeted systemic therapy) investigational or standard of care, within 28 days of the first dose of Avelumab or planned to occur during the study period. Patients receiving bisphosphonates or denosumab will not be excluded.

11. Pregnant or breastfeeding.

12. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organising pneumonia (i.e., bronchiolitis obliterans, cryptogenic organising pneumonia), or evidence of active pneumonitis on screening chest CT scan).

13. Uncontrolled cardiac disease including not limited to symptomatic congestive heart failure, unstable angina pectoris, life-threatening cardiac arrhythmia

14. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5 Grade 3).

15. Use of live attenuated vaccines within 28 days of first dose of Avelumab.

16. Any acute or chronic psychiatric problems that, in the opinion of the Investigator, make the patient ineligible for participation due to compliance concerns.

17. Patients with prior allogeneic stem cell or solid organ transplantation.

18. Patients who are involuntarily incarcerated.

19. Evidence of other malignancy in the past 3 years, with exception of tumours with negligible risk of metastasis or death.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Melanoma and Skin Cancer Trials Limited

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

A/Prof Wen Xu, MBBS, FRACP

Role: STUDY_CHAIR

Princess Alexandra Hospital

Locations

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia

Chris O'Brien Lifehouse

Sydney, New South Wales, Australia

Melanoma Institute Australia

Sydney, New South Wales, Australia

Royal North Shore Hospital

Sydney, New South Wales, Australia

Westmead Hospital

Sydney, New South Wales, Australia

Calvary Mater Hospital

Sydney, New South Wales, Australia

Cancer Care Wollongong

Wollongong, New South Wales, Australia

Royal Brisbane and Woman's Hospital

Brisbane, Queensland, Australia

Cancer Care Service, Bundaberg Base Hospital

Bundaberg, Queensland, Australia

Cairns Hospital

Cairns, Queensland, Australia

Cancer Care Service, Hervey Bay Hospital

Hervey Bay, Queensland, Australia

Mackay Hospital and Health Service

Mackay, Queensland, Australia

Tasman Health Care

Southport, Queensland, Australia

Townsville Hospital

Townsville, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Icon Cancer Centre Hobart

Hobart, Tasmania, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Auckland City Hospital

Auckland, , New Zealand

Countries

Australia; New Zealand

Other Identifiers

03.18

Identifier Type: -

Identifier Source: org_study_id