A Phase III Randomized Study of Adjuvant Ipilimumab Anti-CTLA4 Therapy Versus High-Dose Interferon a-2b for Resected High-Risk Melanoma (ECOG E1609)
Trial Purpose and Description
This trial is divided into 2 Arms. You will be randomly assigned to either Arm A or Arm B. Randomization means that you are put into a group by chance. A computer program will place you in one of the study groups. Neither you nor your doctor can choose the group you will be in. You will have an equal chance of being placed in any group. If you are in group 1 (often called "Arm A") you will receive ipilimumab that will be given in 2 stages called induction phase and maintenance phase. In the induction phase, you will receive iplimumab every 3 weeks for a maximum of 4 doses. In the maintenance phase,you will receive iplimumab every 12 weeks (3 months), beginning at week 24, for a maximum of 4 doses (weeks 24, 36, 48, 60). Ipilimumab will be administered by intravenous infusion, a method of putting the drug directly into the bloodstream through a vein. The infusion will take about 90 minutes and will take place at an outpatient facility.
Prior to the infusion, you will have your vital signs measured. During the infusion your vital signs will be measured every 30 minutes and one hour after the infusion has stopped, your vital signs will be measured one more time. If you are in group 2 (often called "Arm B") you will receive interferon Alfa-2b (IFN) that will begiven in 2 stages called induction phase and maintenance phase.
In the induction phase, you will receive interferon Alfa-2b given 5 consecutive days (Monday to Friday)for four weeks by intravenous infusions over 20 minutes. These infusions will be given in the outpatient setting.
In the maintenance phase, you will receive interferon Alfa-2b three times weekly,every other day (Monday, Wednesday, Friday) for 48 weeks by subcutaneous (under the skin) injections. You will be taught how to self administer the IFN subcutaneous injections. You will be asked to keep track of your injections with a written interferon calendar which will be reviewed during visits to your doctor’s office or clinic.
- All patients must have disease that is completely surgically resected in order to be eligible. Patients must have been surgically rendered free of disease with negative margins on resected specimen. Patients rendered free of disease by non-surgical means are not eligible.
- All patients must have disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization. Imaging studies must include a total body PET-CT scan (with or without brain) and brain MRI or CT (if MRI is contraindicated). If PET-CT cannot be done, CT of neck, chest, abdomen, and pelvis should be done. If for some reason a CT cannot be done, an MRI may be done instead. Any other imaging studies if performed (eg, bone scan) must show no evidence of disease.
- Patients must have primary cutaneous melanoma that belong to one of the following AJCC stages (2009 AJCC Melanoma Staging System
- Patients with disease recurrence after adequate surgical excision of the original primary cutaneous melanoma are allowed. Recurrence in the form of in-transit or satellite metastases or distant skin/subcutaneous, nodal or lung metastases that are completely surgically resected with free margins. Recurrence in a regional lymph node basin. Relapsed disease must be completely surgically resected with free margins.
- Patients must be randomized within 84 days (12 weeks) of surgical resection. If more than one surgical procedure is required to render the patient disease-free, the patient must berandomized within 12 weeks of the last surgery.
- Patients must not have received any adjuvant treatment (chemotherapy, biotherapy, or limb perfusion) after the resection(s) that make(s) them eligible for this trial.
- Prior treatment with anti-CTLA4 monoclonal antibodies or prior CTLA-4 inhibitor or agonist or prior CD137 agonist or prior interferon-&alpha is not allowed. Other forms of prior treatment for melanoma (e.g., IL-2, anti-tumor vaccine, chemotherapy)are allowed if given before the resection(s) that make(s) the patient eligible for this trial, butthese must have been completed at least 4 weeks prior to randomization.
- Patients must have ECOG performance status of 0-1
- Patients must not have an active infection requiring current treatment with parenteral antibiotics. Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of Ipilimumab or HDI hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
- Patients must not have a documented history of inflammatory bowel disease (including ulcerative colitis and Crohn&rsquos disease) or diverticulitis (history of diverticulosis is allowed).
- Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemicimmunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids. A history of occasional (but not continuous) use of steroid inhalers is allowed. Replacement doses of steroids for patients with adrenal insufficiency are allowed. Patients who discontinue use of these classes of medication for at least 2 weeks prior to randomization are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study.
- Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis [e.g., Wegener&rsquos Granulomatosis]) motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis) other CNS autoimmune disease (e.g., poliomyelitis, Multiple sclerosis).
- Patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible.Due to the possible effect of treatment with ipilimumab on the immunologic response toinfectious disease vaccines, patients must not have had any infectious disease vaccination (e.g., standard influenza, H1N1 influenza, pneumococcal, meningococcal, tetanus toxoid)within 4 weeks prior to randomization.
- Patients who have other current malignancies are not eligible. Patients with other malignancies are eligible if they have been continuously disease free for > 5 years prior to the time of randomization. Patients with prior history at any time of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ are eligible.
- Patients with prior history of basal or squamous skin cancer are eligible. Patients who have had multiple primary melanomas are eligible.
- Women must not be pregnant or breast-feeding due to the unknown effects of Ipilimumab and HDI on conception and the fetus. All females of childbearing potential must have a blood test or urine study during screening to rule out pregnancy. Please see Section 7.1.5 for required pregnancy testing prior to and during treatment. 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 preventpregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy)should be considered to be of childbearing potential.
- Men of fathering potential and WOCBP must be using an adequate method of contraception to avoidconception/pregnancy throughout the study and for up to 26 weeks after the last dose of ipilimumab or HDI in such a manner that the risk of pregnancy is minimized.
- Men or WOCBP who are unwilling or unable to strictly follow this requirement are not eligible.
- No active or chronic infection with HIV, Hepatitis B, or Hepatitis C due to the unknown effects of ipilimumab. Patients must have negative testing for HIV, HBV, HCV within 4 weeks prior to randomization.
- Eastern Cooperative Oncology Group
- Last Updated:
- Study HIC#: