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Targeted Therapy and Avelumab in Merkel Cell Carcinoma | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

Targeted Therapy and Avelumab in 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

NCT04261855•Melanoma and Skin Cancer Trials Limited

View on ClinicalTrials.gov

Summary

10.17 GoTHAM is intended as a signal-seeking, biomarker, phase Ib/II study that will evaluate the safety and anti-tumour activities of the novel combination of avelumab with 177-Lu-DOTATATE (a type of peptide receptor radionuclide therapy; PRRT) or external beam radiation therapy (EBRT) in patients with metastatic Merkel cell carcinoma (mMCC).

Detailed Description

Despite recent advances with immune checkpoint inhibitors, such as avelumab which has changed the treatment landscape for metastatic Merkel Cell Carcinoma (mMCC), many mMCC patients who attained an initial response exhibit acquired resistance within 1 year. Therefore, novel treatment combinations are needed to improve patient outcome. MCC is an exquisitely radiosensitive tumour and there is emerging data supporting the role of radiation in inducing immunogenic cell death and therefore potentially improving the anti-tumour efficacy when combined with immune checkpoint inhibitors. Peptide receptor radionuclide therapy (PRRT) is used in first-line treatment for neuroendocrine tumours (NETs), by delivering radiation to somatostatin receptor (SSTR) expressing tumour cells. Most NETs, including MCC, express SSTR. Therefore, MCC tumours are ideal candidates for PRRT, and immune checkpoint inhibitor combination approaches with PRRT are highly attractive. The GoTHAM trial is intended as a signal-seeking and biomarker study. It is designed as a prospective, open-labelled, multi-institutional, two-arm, phase Ib/II trial that will evaluate the safety and anti-tumour activity of 177Lu-DOTA-octreotate (LuTate) or external beam radiation therapy (EBRT) in combination with avelumab in patients with mMCC. The primary objective is to evaluate the anti-tumour activity as reflected by PFS rate at 12 months. The LuTate arm of this study is now closed to recruitment.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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.
+2 more criteria

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).
+7 more criteria

Locations (10)

Mid North Coast Cancer Institute - Coffs Harbour Health Campus

Coffs Harbour, New South Wales, Australia

Lake Macquarie Private Hospital

Gateshead, New South Wales, Australia

Gosford Hospital

Gosford, New South Wales, Australia

Wyong Hospital

Hamlyn Terrace, New South Wales, Australia

Royal North Shore Hospital

Sydney, New South Wales, Australia

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Sir Charles Gaidner Hospital

Perth, Western Australia, Australia

Key Dates

Start Date

October 8, 2020

Primary Completion Date

July 1, 2027

Completion Date

July 1, 2027

Last Updated

February 14, 2025

Enrollment

ESTIMATED participants

Conditions

Metastatic Merkel Cell Carcinoma

Interventions

Avelumab

DRUG

External Beam Radiation Therapy (EBRT)

RADIATION

Lutetium-177 (177Lu)-DOTATATE

RADIATION

Contacts

Melanoma and Skin Cancer Trials Coordinator

CONTACT

+61 3 9903 9022 gotham@masc.org.au

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 14, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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