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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04291885
Other study ID # 03.18
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date October 26, 2020
Est. completion date April 1, 2028

Study information

Verified date April 2024
Source Melanoma and Skin Cancer Trials Limited
Contact Melanoma and Skin Cancer Trials Ltd Project officer
Phone +61 3 9903 9022
Email imat@masc.org.au
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 132
Est. completion date April 1, 2028
Est. primary completion date April 1, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Drug:
Avelumab
Avelumab IV infusion
Placebo
Placebo IV infusion

Locations

Country Name City State
Australia Royal Adelaide Hospital Adelaide South Australia
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 Icon Cancer Centre Hobart Hobart Tasmania
Australia Mackay Hospital and Health Service Mackay Queensland
Australia Alfred Hospital Melbourne Victoria
Australia Peter MacCallum Cancer Centre Melbourne Victoria
Australia Port Macquarie Base Hospital Port Macquarie New South Wales
Australia Calvary Mater Hospital Sydney 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 Townsville Hospital Townsville Queensland
Australia Southern Medical Day Care Centre Wollongong New South Wales
Australia Princess Alexandra Hospital Woolloongabba Queensland
New Zealand Auckland City Hospital Auckland

Sponsors (1)

Lead Sponsor Collaborator
Melanoma and Skin Cancer Trials Limited

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type Measure Description Time frame Safety issue
Other Rate of Merkel cell polyomavirus positivity in stage I-III Merkel cell carcinoma 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
Other Correlating whole exome sequencing (WES) and ribonucleic acid (RNA) expression with immunotherapy response and outcomes in early stage MCC 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
Other Correlating immune infiltrates by multiplex immunohistochemistry (IHC) with survival endpoints To address whether immune infiltrates and PD-L1 expression are associated with survival. 24 Months
Other Utility of circulating biomarkers in predicting recurrence in early stage MCC 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
Primary 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 Overall survival (OS) 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
Secondary Disease-specific survival (DSS) 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
Secondary Rate of loco-regional failure free survival (LRFFS) 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
Secondary Distant metastasis-free survival (DMFS) DMFS is defined as the time from treatment initiation to the first evidence of distant metastatic disease. 24 Months
Secondary Treatment toxicity and tolerability as assessed by NCI CTCAE v5.0 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
Secondary Patient-reported quality of life (QoL) as assessed by FACT-M questionnaire 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
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