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

Plain English Summary

Immunotherapy Adjuvant Trial in Patients With Stage I-III Merkel Cell Carcinoma is a Phase 2 clinical trial sponsored by Melanoma and Skin Cancer Trials Limited studying Merkel Cell Carcinoma, Merkel Cell Carcinoma, Stage I, Merkel Cell Carcinoma, Stage II, Merkel Cell Carcinoma, Stage III, Neuroendocrine Tumors, Carcinoma Neuroendocrine Skin. This trial tests if the drug Avelumab, given after initial treatment, can help prevent Merkel cell carcinoma (MCC) from coming back. It is for patients who have had Stage I-III MCC and have completed their initial treatment. Participants will receive either Avelumab or a placebo (a dummy treatment) through an IV infusion, and will be closely monitored. Standard treatment options for preventing MCC recurrence after initial treatment are not always clear, making this trial important. The trial aims to enroll 122 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with a confirmed diagnosis of Stage I-III Merkel cell carcinoma who have finished their initial treatment. Must be 18 years or older and in good general health (ECOG 0-2). Cannot have distant spread of cancer or a history of certain autoimmune diseases or prior immunotherapy targeting PD-1/PD-L1. Women who can become pregnant must have a negative pregnancy test before starting. This trial is studying Merkel Cell Carcinoma, Merkel Cell Carcinoma, Stage I, Merkel Cell Carcinoma, Stage II, Merkel Cell Carcinoma, Stage III, Neuroendocrine Tumors, Carcinoma Neuroendocrine Skin, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how long patients live without their cancer returning, indicating how well the treatment prevents recurrence. The specific primary outcome measures are: Recurrence-free survival (RFS) (24 Months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for effective adjuvant therapies to prevent the recurrence of Merkel cell carcinoma, a rare but aggressive skin cancer. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Merkel Cell Carcinoma, Merkel Cell Carcinoma, Stage I, Merkel Cell Carcinoma, Stage II, Merkel Cell Carcinoma, Stage III, Neuroendocrine Tumors, Carcinoma Neuroendocrine Skin, where improved treatment options are needed.

Investor Insight

This trial investigates a targeted immunotherapy for a rare cancer, potentially expanding the use of Avelumab and signaling a growing market for adjuvant cancer therapies. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, considering your specific cancer stage and overall health. Participation involves receiving IV infusions of either Avelumab or a placebo, and attending regular appointments for check-ups and monitoring. You will need to provide blood samples and potentially archival tumor tissue for analysis. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 122 participants

Interventions

• DRUG: Avelumab — Avelumab IV infusion
• DRUG: Placebo — Placebo IV infusion

Primary Outcomes

• Recurrence-free survival (RFS) (24 Months)

Secondary Outcomes

• 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)

Full 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.

Trial 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
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Merkel Cell Carcinoma
• Skin Cancer
• Neuroendocrine Tumors
• Adjuvant Therapy
• Immunotherapy
• Oncology
• Stage I Cancer
• Stage II Cancer
• Stage III Cancer
• Recurrence Prevention

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