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

April 12, 2024 updated by: Melanoma and Skin Cancer Trials Limited

A Randomised, Placebo-controlled, Phase II Trial of Adjuvant Avelumab in Patients With Stage I-III Merkel Cell Carcinoma

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

132

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Melanoma and Skin Cancer Trials Ltd Project officer
  • Phone Number: +61 3 9903 9022
  • Email: imat@masc.org.au

Study Locations

  • Australia
    • New South Wales
      • Port Macquarie, New South Wales, Australia, 2444
      • Sydney, New South Wales, Australia, 2145
        • Recruiting
        • Westmead Hospital
        • Contact:
        • Principal Investigator:
          • Prof Michael Veness
      • Sydney, New South Wales, Australia, 2065
        • Recruiting
        • Royal North Shore Hospital
        • Contact:
        • Principal Investigator:
          • A/Prof Alexander Guminski
      • Sydney, New South Wales, Australia, 2050
        • Recruiting
        • Chris O'Brien Lifehouse
        • Contact:
        • Principal Investigator:
          • Dr Jenny Lee
      • Sydney, New South Wales, Australia, 2065
        • Recruiting
        • Melanoma Institute Australia
        • Contact:
        • Principal Investigator:
          • Prof Georgina Long
      • Sydney, New South Wales, Australia, 2298
        • Recruiting
        • Calvary Mater Hospital
        • Contact:
        • Principal Investigator:
          • Dr Ina Nordman
      • Wollongong, New South Wales, Australia, 2500
    • Queensland
      • Brisbane, Queensland, Australia, 4029
        • Recruiting
        • Royal Brisbane and Woman's Hospital
        • Contact:
        • Principal Investigator:
          • Dr Melissa Eastgate
      • Bundaberg, Queensland, Australia, 4670
      • Cairns, Queensland, Australia, 4870
      • Hervey Bay, Queensland, Australia, 4655
      • Mackay, Queensland, Australia, 4740
      • Townsville, Queensland, Australia
        • Recruiting
        • Townsville Hospital
        • Contact:
        • Principal Investigator:
          • Dr Daniel Xing
      • Woolloongabba, Queensland, Australia, 4102
        • Recruiting
        • Princess Alexandra Hospital
        • Contact:
        • Principal Investigator:
          • A/Professor Victoria Atkinson
        • Principal Investigator:
          • Dr Wen Xu
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • Royal Adelaide Hospital
        • Contact:
        • Principal Investigator:
          • Prof Michael Brown
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Recruiting
        • Icon Cancer Centre Hobart
        • Contact:
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Peter MacCallum Cancer Centre
        • Contact:
        • Principal Investigator:
          • A/Prof Shahneen Sandhu
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Alfred Hospital
        • Contact:
        • Principal Investigator:
          • Prof Mark Shackleton
  • New Zealand
      • Auckland, New Zealand
        • Recruiting
        • Auckland City Hospital
        • Contact:
          • Dr Gareth Rivalland
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 study entry.
  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. No evidence of other malignancy in the past 3 years, with exception of tumours with negligible risk of metastasis or death.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Avelumab
6 months of Avelumab at a dose of 800mg as a 60-minute intravenous (IV) infusion once every 2 weeks (13 doses)
Drug: Avelumab
Avelumab IV infusion
Other Names:
  • Bavencio
  • anti-PD-L1
Placebo Comparator: Placebo
6 months of Placebo as a 60-minute intravenous (IV) infusion once every 2 weeks (13 doses)
Drug: Placebo
Placebo IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence-free survival (RFS)
Time Frame: 24 Months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 24 Months
Overall survival rates at 12 and 24 months. Overall survival is defined as the time from treatment initiation to the date of death due to any cause.
24 Months
Disease-specific survival (DSS)
Time Frame: 24 Months
Disease-specific survival at 24 months from treatment initiation. Disease-specific survival is the percentage of participants who have not died from Merkel Cell Carcinoma
24 Months
Rate of loco-regional failure free survival (LRFFS)
Time Frame: 24 Months
Rate of loco-regional failure free survival (LRFFS) is defined as the time from treatment initiation to the first recurrence of the loco-regional tumour.
24 Months
Distant metastasis-free survival (DMFS)
Time Frame: 24 Months
DMFS is defined as the time from treatment initiation to the first evidence of distant metastatic disease.
24 Months
Treatment toxicity and tolerability as assessed by NCI CTCAE v5.0
Time Frame: 24 Months
Rate of treatment-related adverse events (AEs). Safety will be measured by serious adverse events (SAEs) and AEs assessed as per NCI CTCAE v5.0, including immune-related adverse events.
24 Months
Patient-reported quality of life (QoL) as assessed by FACT-M questionnaire
Time Frame: 24 Months
FACT-M form (version 4) will be utilised. This will include patient-reported questions relating to physical wellbeing, social/family wellbeing, emotional wellbeing, functional wellbeing and additional patient concerns which are measured from 0-4 (Not at all - Very Much).
24 Months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Merkel cell polyomavirus positivity in stage I-III Merkel cell carcinoma
Time Frame: 24 Months
To identify Merkel cell polyomavirus MCPyV virus status. To correlate viral aetiology-rate of Merkel cell polyomavirus (MCPyV) positivity in pathology specimens in stage I-III Merkel cell carcinoma with outcome from adjuvant treatment.
24 Months
Correlating whole exome sequencing (WES) and ribonucleic acid (RNA) expression with immunotherapy response and outcomes in early stage MCC
Time Frame: 24 Months
To evaluate the relationship between somatic mutations in cancer genes or the total mutation burden of the cancer with immunotherapy response and outcome following adjuvant therapy.
24 Months
Correlating immune infiltrates by multiplex immunohistochemistry (IHC) with survival endpoints
Time Frame: 24 Months
To address whether immune infiltrates and PD-L1 expression are associated with survival.
24 Months
Utility of circulating biomarkers in predicting recurrence in early stage MCC
Time Frame: 24 Months
To identify predictive biomarkers for response and resistance to immunotherapy in patients with stage I-III MCC using archival tissue and peripheral blood.
24 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Melanoma and Skin Cancer Trials Limited

Investigators

  • Study Chair: Wen Xu, MBBS, FRACP, Princess Alexandra Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2020

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

February 6, 2020

First Submitted That Met QC Criteria

February 28, 2020

First Posted (Actual)

March 2, 2020

Study Record Updates

Last Update Posted (Estimated)

April 15, 2024

Last Update Submitted That Met QC Criteria

April 12, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03.18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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