Merkel Cell CarcinomaPhase 2NCT03071406
Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma
A Phase 2 study testing Nivolumab, Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) in people with Merkel Cell Carcinoma and Skin Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 2 sites in United States.
Trial summary
The purpose of this study is to test the effectiveness, safety, and tolerability of the drugs nivolumab plus ipilimumab with or without the addition of stereotactic body radiation therapy (SBRT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Merkel Cell Carcinoma, Skin Cancer
- What is being tested?
- Nivolumab, Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Mar 2017to 19 Sep 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- At least 18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance Status less than 2
- Active disease measurable by CT, MRI or clinical exam.
- Prior chemotherapy or immunotherapy will be allowed if new or persistent measurable site(s) of disease are present.
- Prior radiation therapy will be allowed if there is active measurable disease burden.
- Must be either recurrent, unresectable or Stage IV American Joint Committee on Cancer (AJCC) (7th edition) and have histologically confirmed Merkel cell carcinoma with at least 2 distinct lesions in order to be eligible.
- Must have at least 2 distinct lesions as documented by a complete physical examination or imaging studies within 4 weeks prior to randomization. Imaging studies must include a diagnostic CT scan of the involved disease sites and all known sites of resected disease and brain magnetic resonance (MRI) or CT (brain CT allowable if MRI is contraindicated or if there is no known history of resected brain lesions).
- Tumor tissue from the core biopsy or resected site of disease must be provided for biomarker analyses.
Who cannot join
- History of Grade 3 toxicity or use of infliximab with prior immunotherapy
- Patients with active brain metastasis.
- Active, known, or suspected autoimmune disease. Potential participants with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.
- Patients with prior history of non-Merkel cell carcinoma malignancies are excluded except adequately treated basal cell, squamous cell skin cancer, chronic lymphocytic leukemia or other indolent diseases not requiring therapy; adequately treated, with curative intent, cancer from which the patient is currently in complete remission per investigator's judgment; or patients with history of breast cancer and no evidence of disease on hormonal therapy to prevent recurrence and patients with prostate cancer on adjuvant hormonal therapy with undetectable PSA are eligible.
- A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase 2, Randomized, Multi-institutional Study of Nivolumab and Ipilimumab Versus Nivolumab, Ipilimumab and Stereotactic Body Radiation Therapy for Metastatic Merkel Cell Carcinoma
The purpose of this study is to test the effectiveness, safety, and tolerability of the drugs nivolumab plus ipilimumab with or without the addition of stereotactic body radiation therapy (SBRT). Nivolumab is an antibody (a type of human protein) that is being tested to see if it will stimulate the body's immune system to work against tumor cells. This study will test an investigational use of nivolumab.
- Conditions
- Merkel Cell Carcinoma, Skin Cancer
- Being tested
- Nivolumab, Ipilimumab, Stereotactic Body Radiation Therapy (SBRT)
- Keywords
- Merkel cell carcinoma (MCC), Metastatic, Metastasis, Stereotactic body radiation therapy (SBRT), Immunology, Antibody, Nivolumab, Ipilimumab, Metastatic skin cancer, Cutaneous
- Medical subject headings
- Carcinoma, Merkel Cell, Skin Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called OPDIVO
Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.
IpilimumabDrug
Also called YERVOY
Ipilimumab 1 mg/kg/dose IV q6 weeks.
Stereotactic Body Radiation Therapy (SBRT)Radiation
Also called SBRT
Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Nivolumab + Ipilimumab | Active comparator | Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Receives: Drug: Nivolumab; Drug: Ipilimumab |
| Arm B: Nivolumab + Ipilimumab + SBRT | Active comparator | Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2. Receives: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response
Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR).
Measured: Up to 18 months
Secondary outcomes (2)
Progression Free Survival (PFS)
Median Progression Free Survival with 95% Confidence Interval. Progression is defined as progressive tumor lesions per immune-related Response Evaluation in Solid Tumors (irRECIST) definition, or appearance of one or more new Merkel cell carcinoma lesions, which can be local or distant in location from the irradiated lesions.
Measured: up to 28 months
Overall Survival (OS)
Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause.
Measured: Up to 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2017
- Study start14 Mar 2017
- Primary completion6 Apr 2022
- Study completion19 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Merkel Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomly assigned in a 1:1 ratio to Arm A (nivolumab + ipilimumab), or Arm B (nivolumab + ipilimumab + SBRT).
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Evan Wuthrick, M.D, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03071406
- Sponsor's protocol ID
- MCC-18786
- Other IDs
- CA209-737
- Status last verified
- Feb 2026
- First submitted
- 1 Mar 2017
- Last updated
- 11 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kim S, Wuthrick E, Blakaj D, Eroglu Z, Verschraegen C, Thapa R, Mills M, Dibs K, Liveringhouse C, Russell J, Caudell JJ, Tarhini A, Markowitz J, Kendra K, Wu R, Chen DT, Berglund A, Michael L, Aoki M, Wang MH, Hamaidi I, Cheng P, de la Iglesia J, Slebos RJ, Chung CH, Knepper TC, Moran-Segura CM, Nguyen JV, Perez BA, Rose T, Harrison L, Messina JL, Sondak VK, Tsai KY, Khushalani NI, Brohl AS. Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial. Lancet. 2022 Sep 24;400(10357):1008-1019. doi: 10.1016/S0140-6736(22)01659-2. Epub 2022 Sep 12.
PubMed 36108657Hoogland AI, Brohl AS, Small BJ, Michael L, Wuthrick E, Eroglu Z, Blakaj D, Verschraegen C, Khushalani NI, Jim HSL, Kim S. Quality of life and patient-reported toxicities in patients with advanced Merkel cell carcinoma treated with combined nivolumab and ipilimumab with or without stereotactic body radiation therapy. Cancer Med. 2024 Jul;13(14):e7464. doi: 10.1002/cam4.7464.
PubMed 39021272
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Multi-institutional Study of Nivolumab and Ipilimumab Versus Nivolumab, Ipilimumab and Stereotactic Body Radiation Therapy for Metastatic Merkel Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03071406
- Acronym / sponsor ID
- MCC-18786
- Conditions
- Merkel Cell Carcinoma, Skin Cancer
- Keywords
- Merkel cell carcinoma (MCC), Metastatic, Metastasis, Stereotactic body radiation therapy (SBRT), Immunology, Antibody, Nivolumab, Ipilimumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 14 Mar 2017 (actual)
- Primary completion
- 6 Apr 2022 (actual)
- Study completion
- 19 Sep 2026 (estimated)
- First posted
- 6 Mar 2017 (actual)
- Results
- Posted 19 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the effectiveness, safety, and tolerability of the drugs nivolumab plus ipilimumab with or without the addition of stereotactic body radiation therapy (SBRT). Nivolumab is an antibody (a type of human protein) that is being tested to see if it will stimulate the body's immune system to work against tumor cells. This study will test an investigational use of nivolumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants are randomly assigned in a 1:1 ratio to Arm A (nivolumab + ipilimumab), or Arm B (nivolumab + ipilimumab + SBRT).
| Arm | Type | Receives |
|---|---|---|
| Arm A: Nivolumab + Ipilimumab | Active comparator | Drug: Nivolumab, Drug: IpilimumabNivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. |
| Arm B: Nivolumab + Ipilimumab + SBRT | Active comparator | Drug: Nivolumab, Drug: Ipilimumab, Radiation: Stereotactic Body Radiation Therapy (SBRT)Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- At least 18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance Status less than 2
- Active disease measurable by CT, MRI or clinical exam.
- Prior chemotherapy or immunotherapy will be allowed if new or persistent measurable site(s) of disease are present.
- Prior radiation therapy will be allowed if there is active measurable disease burden.
Key exclusion criteria (5 listed)
- History of Grade 3 toxicity or use of infliximab with prior immunotherapy
- Patients with active brain metastasis.
- Active, known, or suspected autoimmune disease. Potential participants with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.
- Patients with prior history of non-Merkel cell carcinoma malignancies are excluded except adequately treated basal cell, squamous cell skin cancer, chronic lymphocytic leukemia or other indolent diseases not requiring therapy; adequately treated, with curative intent, cancer from which the patient is currently in complete remission per investigator's judgment; or patients with history of breast cancer and no evidence of disease on hormonal therapy to prevent recurrence and patients with prostate cancer on adjuvant hormonal therapy with undetectable PSA are eligible.
- A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
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 |
|---|---|---|
| NivolumabAlso: OPDIVONivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. | Drug | Arm A: Nivolumab + Ipilimumab, Arm B: Nivolumab + Ipilimumab + SBRT |
| IpilimumabAlso: YERVOYIpilimumab 1 mg/kg/dose IV q6 weeks. | Drug | Arm A: Nivolumab + Ipilimumab, Arm B: Nivolumab + Ipilimumab + SBRT |
| Stereotactic Body Radiation Therapy (SBRT)Also: SBRTStereotactic Body Radiation Therapy 24Gy in 3 fractions. | Radiation | Arm B: Nivolumab + Ipilimumab + SBRT |
Primary outcome
Best Overall Response
Time frame: Up to 18 months
Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR).
2 secondary outcomes
Progression Free Survival (PFS)
Time frame: up to 28 months
Overall Survival (OS)
Time frame: Up to 30 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 36108657Kim S, Wuthrick E, Blakaj D, Eroglu Z, Verschraegen C, Thapa R, Mills M, Dibs K, Liveringhouse C, Russell J, Caudell JJ, Tarhini A, Markowitz J, Kendra K, Wu R, Chen DT, Berglund A, Michael L, Aoki M, Wang MH, Hamaidi I, Cheng P, de la Iglesia J, Slebos RJ, Chung CH, Knepper TC, Moran-Segura CM, Nguyen JV, Perez BA, Rose T, Harrison L, Messina JL, Sondak VK, Tsai KY, Khushalani NI, Brohl AS. Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial. Lancet. 2022 Sep 24;400(10357):1008-1019. doi: 10.1016/S0140-6736(22)01659-2. Epub 2022 Sep 12.
- Derived from this study: PubMed 39021272Hoogland AI, Brohl AS, Small BJ, Michael L, Wuthrick E, Eroglu Z, Blakaj D, Verschraegen C, Khushalani NI, Jim HSL, Kim S. Quality of life and patient-reported toxicities in patients with advanced Merkel cell carcinoma treated with combined nivolumab and ipilimumab with or without stereotactic body radiation therapy. Cancer Med. 2024 Jul;13(14):e7464. doi: 10.1002/cam4.7464.
- Moffitt Cancer Center Clinical Trials websiteLink provided by the sponsor.
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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.
Evan Wuthrick, M.D principal investigator
H. Lee Moffitt Cancer Center and Research Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) in people with Merkel Cell Carcinoma and Skin Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 2 sites in United States.
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 8 inclusion and 5 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 11 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 2 sites in United States. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 19 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Best Overall Response (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03071406, which also lists 2 linked publications.
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 11 Mar 2026.