Merkel Cell Carcinoma, Skin Cancer
Conditions
Keywords
Merkel cell carcinoma (MCC), Metastatic, Metastasis, Stereotactic body radiation therapy (SBRT), Immunology, Antibody, Nivolumab, Ipilimumab, Metastatic skin cancer, Cutaneous
Brief 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). 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.
Interventions
DRUGIpilimumab
Ipilimumab 1 mg/kg/dose IV q6 weeks.
RADIATIONStereotactic Body Radiation Therapy (SBRT)
Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
DRUGNivolumab
Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are randomly assigned in a 1:1 ratio to Arm A (nivolumab + ipilimumab), or Arm B (nivolumab + ipilimumab + SBRT).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | Up to 18 months | Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | up to 28 months | 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. |
| Overall Survival (OS) | Up to 30 months | Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREvan Wuthrick, M.D
H. Lee Moffitt Cancer Center and Research Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Nivolumab + Ipilimumab Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.
Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.
Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks. | 25 |
| Arm B: Nivolumab + Ipilimumab + 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.
Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.
Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks.
Stereotactic Body Radiation Therapy (SBRT): Stereotactic Body Radiation Therapy 24Gy in 3 fractions. | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Arm A: Nivolumab + Ipilimumab | Total | Arm B: Nivolumab + Ipilimumab + SBRT |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 40 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 10 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 50 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 50 Participants | 25 Participants |
| Region of Enrollment United States | 25 participants | 50 participants | 25 participants |
| Sex: Female, Male Female | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Male | 20 Participants | 39 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 25 | 15 / 25 |
| other Total, other adverse events | 25 / 25 | 25 / 25 |
| serious Total, serious adverse events | 13 / 25 | 13 / 25 |
Outcome results
Primary
Best Overall Response
Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR).
Time frame: Up to 18 months
Population: Evaluable participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Nivolumab + Ipilimumab | Best Overall Response | 18 Participants |
| Arm B: Nivolumab + Ipilimumab + SBRT | Best Overall Response | 12 Participants |
Secondary
Overall Survival (OS)
Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause.
Time frame: Up to 30 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Nivolumab + Ipilimumab | Overall Survival (OS) | 29.9 months |
| Arm B: Nivolumab + Ipilimumab + SBRT | Overall Survival (OS) | 16 months |
Secondary
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.
Time frame: up to 28 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Nivolumab + Ipilimumab | Progression Free Survival (PFS) | 27.7 months |
| Arm B: Nivolumab + Ipilimumab + SBRT | Progression Free Survival (PFS) | 7.6 months |