NCT04261855

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

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 19 (estimated)
• Sponsor: Melanoma and Skin Cancer Trials Limited · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Metastatic Merkel Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Avelumab	All patients will receive avelumab intravenously (IV) at 10 mg/kg every 2 weeks for 24 months or until unacceptable toxicity or evidence of disease progression
RADIATION	External Beam Radiation Therapy (EBRT)	Patients allocated to Arm A will receive EBRT on 2 occasions, 8-10 weeks apart
RADIATION	Lutetium-177 (177Lu)-DOTATATE	Patients allocated to Arm B will receive 177-Lu-DOTATATE treatment on 2 occasions, 8-10 weeks apart. This treatment arm is now closed to recruitment.

Timeline

• Start date: 2020-10-08
• Primary completion: 2026-12-01
• Completion: 2027-12-01
• First posted: 2020-02-10
• Last updated: 2026-03-27

Locations

10 sites across 1 country: Australia