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

Neuroendocrine Tumors Clinical Trial

— I-MAT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04291885
• Other study ID #: 03.18
• Status: Recruiting
• Phase: Phase 2
• 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
• 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.

Related Conditions & MeSH terms

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

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