NCT04291885

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.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
122

participants targeted

Target at P75+ for phase_2

Timeline
49mo left

Started Oct 2020

Longer than P75 for phase_2

Geographic Reach
2 countries

20 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress58%
Oct 2020Apr 2030

First Submitted

Initial submission to the registry

February 6, 2020

Completed
25 days until next milestone

First Posted

Study publicly available on registry

March 2, 2020

Completed
8 months until next milestone

Study Start

First participant enrolled

October 26, 2020

Completed
6.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2027

Expected
3.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2030

Last Updated

April 9, 2026

Status Verified

April 1, 2025

Enrollment Period

6.4 years

First QC Date

February 6, 2020

Last Update Submit

April 7, 2026

Conditions

Merkel Cell Carcinoma, Stage IIINeuroendocrine TumorsCarcinoma Neuroendocrine SkinMerkel Cell Carcinoma, Stage IMerkel Cell CarcinomaMerkel Cell Carcinoma, Stage II

Outcome Measures

Primary Outcomes (1)

  • Recurrence-free survival (RFS)

    Recurrence-free survival (RFS) as the primary endpoint, is anticipated to be analysed over an average planned follow-up of 3.5 years. An analysis of RFS at the 24 month time point of follow-up will also be conducted as it is anticipated that the minimum follow-up for participants will be 24 months and the sample size rationale utilises RFS rates at 24 months in historical controls. RFS is defined as the time from treatment initiation until the first date of any signs or symptoms of recurrence of tumour.

    24 Months

Secondary Outcomes (6)

  • Overall survival (OS)

    24 Months

  • Disease-specific survival (DSS)

    24 Months

  • Rate of loco-regional failure free survival (LRFFS)

    24 Months

  • Distant metastasis-free survival (DMFS)

    24 Months

  • Treatment toxicity and tolerability as assessed by NCI CTCAE v5.0

    24 Months

  • +1 more secondary outcomes

Other Outcomes (4)

  • Rate of Merkel cell polyomavirus positivity in stage I-III Merkel cell carcinoma

    24 Months

  • Correlating whole exome sequencing (WES) and ribonucleic acid (RNA) expression with immunotherapy response and outcomes in early stage MCC

    24 Months

  • Correlating immune infiltrates by multiplex immunohistochemistry (IHC) with survival endpoints

    24 Months

  • +1 more other outcomes

Study Arms (2)

Avelumab

EXPERIMENTAL

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

Drug: Avelumab

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

AvelumabDRUG

Avelumab IV infusion

Also known as: anti-PD-L1, Bavencio
Avelumab
PlaceboDRUG

Placebo IV infusion

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).
  • Absence of distant metastatic disease on baseline 18-Fludeoxyglucose (18FDG) - Positron Emission Tomography (PET) / Computed Tomography (CT) scan.
  • years of age or older.
  • Eastern Cooperative Oncology Group (ECOG) of 0 - 2.
  • Willing and able to provide written informed consent and comply with all study requirements.
  • Adequate haematological, liver and renal function as determined by the screening laboratory values outlined in the protocol obtained within 14 days prior to randomisation.
  • Agreeable to collection of archival tumour material. Where possible, the most recently acquired tumour specimen should be provided.
  • Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to the start of treatment.

You may not qualify if:

  • 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.
  • Prior treatment with an agent that blocks the PD-1/PD-L1 pathway.
  • 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.
  • Prior treatment with other immune-modulating agents that was within fewer than 28 days prior to the first dose of Avelumab.
  • Active infection requiring antibiotics within 7 days of cycle 1 day 1 of study drug dose.
  • Active tuberculosis.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • 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.
  • 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
  • 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.
  • Pregnant or breastfeeding.
  • 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).
  • Uncontrolled cardiac disease including not limited to symptomatic congestive heart failure, unstable angina pectoris, life-threatening cardiac arrhythmia
  • 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).
  • Use of live attenuated vaccines within 28 days of first dose of Avelumab.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Chris O'Brien Lifehouse

Sydney, New South Wales, 2050, Australia

Location

Melanoma Institute Australia

Sydney, New South Wales, 2065, Australia

Location

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Calvary Mater Hospital

Sydney, New South Wales, 2298, Australia

Location

Cancer Care Wollongong

Wollongong, New South Wales, 2500, Australia

Location

Royal Brisbane and Woman's Hospital

Brisbane, Queensland, 4029, Australia

Location

Cancer Care Service, Bundaberg Base Hospital

Bundaberg, Queensland, 4670, Australia

Location

Cairns Hospital

Cairns, Queensland, 4870, Australia

Location

Cancer Care Service, Hervey Bay Hospital

Hervey Bay, Queensland, 4655, Australia

Location

Mackay Hospital and Health Service

Mackay, Queensland, 4740, Australia

Location

Tasman Health Care

Southport, Queensland, 4215, Australia

Location

Townsville Hospital

Townsville, Queensland, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Icon Cancer Centre Hobart

Hobart, Tasmania, 7000, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3000, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Auckland City Hospital

Auckland, New Zealand

Location

MeSH Terms

Conditions

Carcinoma, Merkel CellNeuroendocrine Tumors

Interventions

avelumab

Condition Hierarchy (Ancestors)

Polyomavirus InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsCarcinoma, NeuroendocrineNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Study Officials

  • A/Prof Wen Xu, MBBS, FRACP

    Princess Alexandra Hospital

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Double-blind
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 6, 2020

First Posted

March 2, 2020

Study Start

October 26, 2020

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

April 30, 2030

Last Updated

April 9, 2026

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations

AU(19)NZ(1)