Combining Avelumab with Radiation Therapy for Merkel Cell Carcinoma

A Phase Ib/II Study of Combination Avelumab With Peptide Receptor Radionuclide Therapy or Conventional Fractionated Radiotherapy in Patients With Metastatic Merkel Cell Carcinoma

This study is testing if combining avelumab with radiation therapy can help people with advanced Merkel cell carcinoma live longer without their cancer getting worse.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 19 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Melanoma and Skin Cancer Trials Limited (Academic / other)
• Drugs / interventions: avelumab, chemotherapy, radiation, prednisone
• Locations: 10 sites (Coffs Harbour, New South Wales and 9 other locations)
• Trial ID: NCT04261855 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and anti-tumor activity of avelumab combined with either Lutetium-177 DOTATATE or external beam radiation therapy in patients with metastatic Merkel cell carcinoma (mMCC). The study aims to address the issue of acquired resistance to immune checkpoint inhibitors by exploring novel treatment combinations. It is designed as a prospective, open-label, multi-institutional, two-arm trial, focusing on the progression-free survival rate at 12 months as the primary endpoint. The trial includes patients who have measurable disease and are treatment-naïve, ensuring a focused assessment of the new treatment approach.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with histologically confirmed metastatic Merkel cell carcinoma who have not received prior systemic therapy.

Not a fit: Patients with prior systemic therapy for unresectable or metastatic Merkel cell carcinoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a new effective treatment option for patients with metastatic Merkel cell carcinoma.

How similar studies have performed: Other studies have shown promise in combining immune checkpoint inhibitors with radiation therapy, suggesting potential success for this novel approach.

Eligibility criteria

Inclusion Criteria:

* Patient is 18 years of age or older and who has provided written informed consent.
* Patient has histologically confirmed metastatic MCC.
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 .
* Willing and able to comply with all study protocol requirements for the duration of the study.
* Patient must have measurable disease by CT or MRI per RECIST version 1.1 criteria.
* Patient is treatment naïve (no prior systemic therapy for unresectable or metastatic MCC). Note that prior chemotherapy is permitted in the adjuvant setting for loco-regional disease. Prior radiation is permitted for treatment of the primary or loco-regional disease.
* At least 2 weeks since the completion of prior therapy, including surgery or radiotherapy.
* Screening laboratory values, obtained within 14 days prior to registration/randomisation must meet the criteria specified in the protocol.
* Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception
* WOCBP must have a negative serum or urine pregnancy test within within 7 days prior to the start of avelumab treatment and should be performed every 4 weeks in line with other safety bloods or clinical reviews.
* Male patients who are sexually active with a WOCBP must use any contraceptive method with a failure rate of less than 1% per year.
* Patient must be agreeable to have archival tumour material collected

Exclusion Criteria:

* Patient is excluded if they have ever had any brain or leptomeningeal metastases.
* Prior exposure to immune checkpoint inhibitors (e.g. anti-CTLA-4, anti-PD-1/PD-L1/PD-L2, etc.) or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
* Prior exposure to 177Lu-DOTATATE.
* Prior malignancy within the previous 2 years, except for locally curable cancers that have been apparently cured (e.g. basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, colon, bladder or breast).
* Life expectancy of 6 months or less.
* An active, known or suspected autoimmune disease that might lead to clinically significant deterioration as per the investigator when receiving an immunostimulatory agent. Patients are permitted to enrol if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger. They are permitted to enrol if they have clinically quiescent auto-immune conditions not requiring immunomodulation beyond low dose steroids (ie \<10mg per day of prednisolone or equivalent) or topical therapies (including mesalazine or steroid enemas).
* Current use of immunosuppressive medication, with exceptions detailed in the protocol
* Prior organ transplantation, including allogeneic stem-cell transplantation.
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
* Positive test for hepatitis B virus (HBV) surface antigen and/or confirmatory hepatitis C virus (HCV) RNA (if anti-HCV antibody tested positive at Screening).
* Pregnant or breastfeeding.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
* Persisting toxicity related to prior therapy (NCI CTCAE v5.0 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on Investigator's judgement are acceptable.
* Known prior severe hypersensitivity to investigational product or any component in its formulations, including known hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade 3).
* Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable.
* Use of any live vaccines against infectious diseases (e.g., influenza, varicella, etc.) within 30 days of registration.

Where this trial is running

Coffs Harbour, New South Wales and 9 other locations

• Mid North Coast Cancer Institute - Coffs Harbour Health Campus — Coffs Harbour, New South Wales, Australia (Recruiting)
• Lake Macquarie Private Hospital — Gateshead, New South Wales, Australia (Recruiting)
• Gosford Hospital — Gosford, New South Wales, Australia (Recruiting)
• Wyong Hospital — Hamlyn Terrace, New South Wales, Australia (Recruiting)
• Royal North Shore Hospital — Sydney, New South Wales, Australia (Recruiting)
• Royal Brisbane and Women's Hospital — Brisbane, Queensland, Australia (Recruiting)
• Princess Alexandra Hospital — Brisbane, Queensland, Australia (Recruiting)
• Royal Adelaide Hospital — Adelaide, South Australia, Australia (Recruiting)
• Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia (Recruiting)
• Sir Charles Gaidner Hospital — Perth, Western Australia, Australia (Recruiting)

Study contacts

• Study coordinator: Melanoma and Skin Cancer Trials Coordinator

Conditions Metastatic Merkel Cell Carcinoma; radiotherapy; peptide receptor radionuclide therapy; neuroendocrine tumour; rare cancer; merkel cell; carcinoma; immunotherapy