A Pilot Study of Ipilimumab in Subjects With Stage IV Melanoma Receiving Palliative Radiation Therapy
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.
- drug : Ipilimumab
- radiation : Radiation Therapy
Ages Eligible For Study:
1. 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. 2. 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 2. - Life expectancy of >= 16 weeks. - Subjects must have baseline (screening/baseline) radiographic images, (e.g. brain, chest, abdomen, pelvis, and bone scans with specific imaging tests to be determined by the attending physician) within 6 weeks of initiation of ipilimumab. - Required values for initial laboratory tests: - WBC: >= 2000/uL (~ 2 x 10^9/L) - ANC: >= 1000/uL (~ 1 x 10^9/L) - Platelets: >= 75 x 10^3/uL (~ 75 x 10^9/L) - Hemoglobin: >= 9 g/dL (~ 80 g/L; may be transfused) - Creatinine: ~ 2 x ULN - AST/ALT: ~ 2.5 x ULN for subjects without liver metastasis ~ 5 times for liver metastases - Bilirubin: ~ 2.0 x ULN (except for subjects with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL) - No active or chronic infection with HIV, Hepatitis B, or Hepatitis C. - Two or more measurable sites of disease (>= 1.5 cm) which include the disease site that requires palliative radiation therapy as well as >= 1 other disease site outside of the planned radiation therapy field. 3. Age and Sex - Men and women, at least 18 years of age. - Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized. - WOCBP include any female who has experienced menarche and who has undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post-menopausal is defined as: - Amenorrhea >= 12 consecutive months without another cause, or - For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL - Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product. c) Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.