A Pilot Study of Ipilimumab in Subjects With Stage IV Melanoma Receiving Palliative Radiation Therapy
Overview
- Phase
- Phase 2
- Intervention
- Ipilimumab
- Conditions
- Melanoma
- Sponsor
- Stanford University
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- Safety Measurement - Percentage of Patients Experiencing Serious Adverse Events (SAEs) in the First 4 Months of Treatment.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
To determine the safety of local palliative radiation therapy used in combination with anti-CTLA-4 immunotherapy.
Detailed Description
This is a single institution, open-label, pilot study of palliative radiation therapy (RT) combined with ipilimumab in patients with stage IV melanoma. The primary objective of this study is to assess the safety of combining ipilimumab with palliative RT in patients with Stage IV melanoma. Secondary objectives are a) to assess the induction of anti-melanoma immune responses using laboratory correlative studies of T cell responses to melanoma antigens, and b) to compare tumor response rates and duration of response at unirradiated sites with responses in patients with Stage IV disease treated with ipilimumab alone on expanded access study CA184045. In this study, ipilimumab will be administered as recently approved by the FDA (3 mg/kg iv every 3 weeks for a total of 4 treatments). Palliative RT will start within 2 days of the first ipilimumab dose. Patients will be seen at least every 12 weeks for follow-up following completion of ipilimumab therapy until progression of disease by imaging criteria or increased symptomatology that requires another therapy. A total of 20 patients with previously treated unresectable metastatic melanoma requiring palliative radiation therapy will be treated on this pilot study over approximately 18 months. All subjects who receive study drug will be monitored for safety. Relevant tumor imaging studies will be obtained at baseline, 2-4 weeks following the 4th/last dose of ipilimumab, and then every 12 weeks until disease progression. This study will provide the safety data (and possibly early efficacy signals) needed to proceed with a randomized Phase II study for proof of principle. If compelling data is obtained supporting this IT + RT vaccine strategy, this approach will be extended to other solid tumor types.
Investigators
Susan Knox
Associate Professor of Radiation Oncology
Stanford University
Eligibility Criteria
Inclusion Criteria
- •Signed Written Informed Consent
- •Before any study procedures are performed, subjects (or their legally acceptable representatives) will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel.
- •Target Population
- •Histologically confirmed Stage IV melanoma.
- •Must have failed at least one systemic therapy for malignant melanoma or be intolerant to at least one prior systemic treatment.
- •Subjects with asymptomatic brain metastases are eligible. (Systemic steroids should be avoided if possible, or the subject should be stable on the lowest clinically effective dose, as steroids as they may interfere with the activity of ipilimumab if administered at the time of the first ipilimumab dose.)
- •Primary ocular and mucosal melanomas are allowed.
- •Must be at least 28 days since treatment with chemotherapy, biochemotherapy, surgery, radiation, or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Life expectancy of ≥ 16 weeks.
Exclusion Criteria
- •Sex and Reproductive Status
- •WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 8 weeks after the last dose of investigational product.
- •WOCBP using a prohibited contraceptive method.
- •Women who are pregnant or breastfeeding.
- •Women with a positive pregnancy test on enrollment or before investigational product administration.
- •Target Disease Exceptions
- •Subjects on any other systemic therapy for cancer, including any other experimental treatment.
- •Prior treatment with an anti-CTLA-4 antibody if treatment failure was due to adverse events (AEs). If a subject was discontinued from the prior anti-CTLA-4 treatment due to an AE or serious adverse event (SAE), regardless of the type of event, that discontinuation constitutes an exclusion criterion. If AEs were serious enough to require a subject's withdrawal from prior treatment, the subject should be excluded from this study.
- •A history of AEs with prior IL-2 or Interferon will not preclude subjects from entering the current study.
- •Subjects who relapsed in study MDX010-16 are not eligible for this study.
Arms & Interventions
Ipilimumab Treatment + Radiation Therapy
Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1 to 2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2 to 4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease.
Intervention: Ipilimumab
Ipilimumab Treatment + Radiation Therapy
Ipilimumab (BMS-734016, MDX010, MDX-CTLA4, Yervoy) will be administered as standard of care with base dose of 3 mg/kg iv over approximately 90 minutes every 3 weeks for a total of 4 treatments. Palliative radiation therapy to 1 to 2 sites of disease will start within 5 days of the first ipilimumab dose. Subjects will have follow up visits 2 to 4 weeks after the last ipilimumab dose and then every 3 months (±2 weeks) thereafter until progression of disease.
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Safety Measurement - Percentage of Patients Experiencing Serious Adverse Events (SAEs) in the First 4 Months of Treatment.
Time Frame: 4 months
Serious adverse events (SAEs) defined as untoward medical occurrence that at any dose: results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires in subject hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, may jeopardize the subject or may require intervention to prevent one of the other serious outcomes listed in the definition above.)
Secondary Outcomes
- Response Rate(2 to 4 weeks after last ipilimumab dose then every 3 months +/- 2 weeks until progression of disease)
- Overall Survival(2 to 4 weeks after last ipilimumab dose then every 3 months +/- 2 weeks until progression of disease)
- Duration of Complete Response(2 to 4 weeks after last ipilimumab dose then every 3 months +/- 2 weeks until progression of disease)
- Duration of Partial Response.(2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.)
- Stable Disease(2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.)
- Median Time to Complete Response or Partial Response(2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.)
- Progression-free Survival (PFS)(2 to 4 weeks after last ipilimumab and then every 3 months until disease progression.)