Targeted Therapy and Avelumab in Merkel Cell Carcinoma

NCT04261855 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 10.17
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 10

Brief 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).

Conditions

Metastatic Merkel Cell Carcinoma

Keywords

radiotherapy; peptide receptor radionuclide therapy; neuroendocrine tumour; rare cancer; merkel cell; carcinoma; immunotherapy; merkel cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) at 12 months

  To evaluate the anti-tumour activity as reflected by PFS rate at 12 months. PFS is defined as the time from treatment initiation until the first date of documented radiographic progression or death due to any cause, whichever occurs first. The radiographic progression will be assessed by the Investigator according to RECIST v1.1.

  3 years

Secondary Outcomes (5)

• Progression Free Survival (PFS) at 24 months

  4 years

• Overall Survival (OS) at 12 and 24 months

  4 years

• Best Objective Response Rate (ORR) according to RECIST v1.1

  4 years

• The safety and tolerability of 177Lu-DOTATATE or EBRT in combination with avelumab.

  4 years

• Rate of treatment discontinuation due to toxicity

  4 years

Study Arms (2)

Arm A

EXPERIMENTAL

Avelumab plus External Beam Radiation Therapy (EBRT)

Drug: Avelumab; Radiation: External Beam Radiation Therapy (EBRT)

Arm B

EXPERIMENTAL

Avelumab plus Lutetium-177 (177Lu)-DOTATATE This treatment arm is now closed to recruitment

Drug: Avelumab; Radiation: Lutetium-177 (177Lu)-DOTATATE

Interventions

Avelumab DRUG

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

Also known as: Bavencio, Anti-PD-L1

Arm A; Arm B

Lutetium-177 (177Lu)-DOTATATE RADIATION

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.

Also known as: Peptide Receptor Radionuclide Therapy (PRRT), Lutathera

Arm B

External Beam Radiation Therapy (EBRT) RADIATION

Patients allocated to Arm A will receive EBRT on 2 occasions, 8-10 weeks apart

Also known as: Radiotherapy

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Melanoma and Skin Cancer Trials Limited: lead

Study Sites (10)

Mid North Coast Cancer Institute - Coffs Harbour Health Campus

Coffs Harbour, New South Wales, 2450, Australia

Location

Lake Macquarie Private Hospital

Gateshead, New South Wales, 2290, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Wyong Hospital

Hamlyn Terrace, New South Wales, 2259, Australia

Location

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Sir Charles Gaidner Hospital

Perth, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell; Neuroendocrine Tumors; Carcinoma

Interventions

avelumab; Radiotherapy; Lutetium-177; lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Prof Shahneen Sandhu, MBBS, FRACP

  Peter MacCallum Cancer Centre, Australia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The LuTate treatment arm is now closed to recruitment

Study Record Dates

• First Submitted: February 6, 2020
• First Posted: February 10, 2020
• Study Start: October 8, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (10)