Metastatic Merkel Cell CarcinomaPhase 1/2GoTHAMNCT04261855
Targeted Therapy and Avelumab in Merkel Cell Carcinoma
A Phase 1/2 study testing Avelumab, External Beam Radiation Therapy (EBRT) and Lutetium-177 (177Lu)-DOTATATE in people with Metastatic Merkel Cell Carcinoma, run by Melanoma and Skin Cancer Trials Limited at 10 sites in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Merkel Cell Carcinoma
- What is being tested?
- Avelumab, External Beam Radiation Therapy (EBRT) and Lutetium-177 (177Lu)-DOTATATE
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 10 sitesAustralia
- Study dates
- 8 Oct 2020to Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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).
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- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Australia10 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Royal Brisbane and Women's Hospital
Brisbane, Queensland, 4029
Princess Alexandra Hospital
Brisbane, Queensland, 4102
Mid North Coast Cancer Institute - Coffs Harbour Health Campus
Coffs Harbour, New South Wales, 2450
Lake Macquarie Private Hospital
Gateshead, New South Wales, 2290
Gosford Hospital
Gosford, New South Wales, 2250
Wyong Hospital
Hamlyn Terrace, New South Wales, 2259
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Sir Charles Gaidner Hospital
Perth, Western Australia, 6009
Royal North Shore Hospital
Sydney, New South Wales, 2065
About this study
Official title: A Phase Ib/II Study of Combination Avelumab With Peptide Receptor Radionuclide Therapy or Conventional Fractionated Radiotherapy in Patients With Metastatic Merkel Cell Carcinoma
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).
Read the 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
- Being tested
- Avelumab, External Beam Radiation Therapy (EBRT), Lutetium-177 (177Lu)-DOTATATE
- Keywords
- radiotherapy, peptide receptor radionuclide therapy, neuroendocrine tumour, rare cancer, merkel cell, carcinoma, immunotherapy, merkel cell carcinoma
- Medical subject headings
- Carcinoma, Merkel Cell, Neuroendocrine Tumors, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
Also called Bavencio, Anti-PD-L1
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
External Beam Radiation Therapy (EBRT)Radiation
Also called Radiotherapy
Patients allocated to Arm A will receive EBRT on 2 occasions, 8-10 weeks apart
Lutetium-177 (177Lu)-DOTATATERadiation
Also called Peptide Receptor Radionuclide Therapy (PRRT), Lutathera
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Avelumab plus External Beam Radiation Therapy (EBRT) Receives: 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 Receives: Drug: Avelumab; Radiation: Lutetium-177 (177Lu)-DOTATATE |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (5)
Progression Free Survival (PFS) at 24 months
Time to disease progression including rate at specific landmark timepoint of 24 months.
Measured: 4 years
Overall Survival (OS) at 12 and 24 months
OS rates at specific landmark timepoints of 12 and 24 months. OS is defined as the time from treatment initiation to the date of death due to any cause.
Measured: 4 years
Best Objective Response Rate (ORR) according to RECIST v1.1
To evaluate best ORR according to response evaluation criteria in solid tumours version 1.1 (RECIST v1.1). ORR is defined as PR or CR at any stage from time of treatment initiation according to RECIST v1.1.
Measured: 4 years
The safety and tolerability of 177Lu-DOTATATE or EBRT in combination with avelumab.
Rate of treatment-related adverse events (AEs). Safety will be measured by serious adverse events (SAEs) and AEs assessed using the NCI CTCAE v5.0.
Measured: 4 years
Rate of treatment discontinuation due to toxicity
This is defined as the proportion of patients who discontinue with treatment due to treatment-related toxicity.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study start8 Oct 2020
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Merkel Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The LuTate treatment arm is now closed to recruitment
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Melanoma and Skin Cancer Trials Limited
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Prof Shahneen Sandhu, MBBS, FRACP, Study chair, Peter MacCallum Cancer Centre, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04261855
- Sponsor's protocol ID
- 10.17
- Acronym
- GoTHAM
- Status last verified
- Mar 2026
- First submitted
- 6 Feb 2020
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of Combination Avelumab With Peptide Receptor Radionuclide Therapy or Conventional Fractionated Radiotherapy in Patients With Metastatic Merkel Cell Carcinoma
- ClinicalTrials.gov ID
- NCT04261855
- Acronym / sponsor ID
- GoTHAM / 10.17
- Conditions
- Metastatic Merkel Cell Carcinoma
- Keywords
- radiotherapy, peptide receptor radionuclide therapy, neuroendocrine tumour, rare cancer, merkel cell, carcinoma, immunotherapy, merkel cell carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- Melanoma and Skin Cancer Trials LimitedUniversity, hospital or other
- Study start
- 8 Oct 2020 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 10 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The LuTate treatment arm is now closed to recruitment
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Avelumab, Radiation: External Beam Radiation Therapy (EBRT)Avelumab plus External Beam Radiation Therapy (EBRT) |
| Arm B | Experimental | Drug: Avelumab, Radiation: Lutetium-177 (177Lu)-DOTATATEAvelumab plus Lutetium-177 (177Lu)-DOTATATE This treatment arm is now closed to recruitment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvelumabAlso: Bavencio, Anti-PD-L1All 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 | Drug | Arm A, Arm B |
| External Beam Radiation Therapy (EBRT)Also: RadiotherapyPatients allocated to Arm A will receive EBRT on 2 occasions, 8-10 weeks apart | Radiation | Arm A |
| Lutetium-177 (177Lu)-DOTATATEAlso: Peptide Receptor Radionuclide Therapy (PRRT), LutatheraPatients 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. | Radiation | Arm B |
Primary outcome
Progression Free Survival (PFS) at 12 months
Time frame: 3 years
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.
5 secondary outcomes
Progression Free Survival (PFS) at 24 months
Time frame: 4 years
Overall Survival (OS) at 12 and 24 months
Time frame: 4 years
Best Objective Response Rate (ORR) according to RECIST v1.1
Time frame: 4 years
The safety and tolerability of 177Lu-DOTATATE or EBRT in combination with avelumab.
Time frame: 4 years
Rate of treatment discontinuation due to toxicity
Time frame: 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof Shahneen Sandhu, MBBS, FRACP study chair
Peter MacCallum Cancer Centre, Australia
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Avelumab, External Beam Radiation Therapy (EBRT) and Lutetium-177 (177Lu)-DOTATATE in people with Metastatic Merkel Cell Carcinoma, run by Melanoma and Skin Cancer Trials Limited at 10 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) at 12 months (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.