Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery
- Conditions
- High-risk resected melanomaMedDRA version: 18.0Level: LLTClassification code 10025651Term: Malignant melanoma excisionSystem Organ Class: 100000004865Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-004257-29-Outside-EU/EEA
- Lead Sponsor
- ational Cancer Institute
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 1545
1.Age > 18 years.
2. 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.
3. Patients must have primary cutaneous melanoma that belong to one of the following AJCC stages: IIIB, IIIC, or IV (M1a or M1b). Patients with stage IV melanoma must have normal LDH and either distant skin, subcutaneous, lymph node or lung metastases, but no other visceral metastases in order to be eligible. For patients with resected stage IV melanoma, LDH within the institutional upper limit of normal (ULN) must be documented within 4 weeks prior to randomization.
4. Patients with disease recurrence after adequate surgical excision of the original primary cutaneous/unknown primary melanoma are allowed even if they don’t fit the strict staging criteria, but only as follows:
• Recurrence in a regional lymph node basin after a prior complete lymph node dissection. Relapsed disease must be completely surgically resected with free margins.
• 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 with unknown primary melanoma (Tx) who present with cutaneous, subcutaneous, nodal and/or lung metastases that are completely surgically resected with free margins are allowed. These patients are allowed even if they don’t fit the strict staging criteria. For stage IV patients LDH within the institutional ULN must be documented within 4 weeks prior to randomization (M1c is not eligible).
All subjects should be classified as IIIB, IIIC, M1a or M1b including subjects with disease recurrence after adequate surgical excision of the original primary melanoma. That is the treating team/physician investigator should review an overall TNM status (that includes primary tumor presentation and disease recurrence status) and provide a designation of IIIB, IIIC, M1a or M1b.
5. 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 be randomized within 12 weeks of the last surgery. Patients with clinically positive lymph nodes for melanoma involvement or those with positive lymph nodes identified through lymphoscintigraphic and/or dye lymphographic techniques in the groin, axilla, or neck should have additional lymphadenectomy in those sites. See Section 5.1 and Appendix VII for suggested guidelines on surgical management. The complete lymph node dissection procedure would be considered as the last surgery in counting the 84 days unless a subsequent surgical procedure(s) was cli
1. 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. Previous radiation therapy, including after the surgical resection, is allowed as long as 21 days have elapsed between the radiation and initiation of this adjuvant systemic therapy.
2. Prior treatment with anti-CTLA4 monoclonal antibodies or prior CTLA-4 inhibitor or agonist or prior CD137 agonist or prior interferon-a 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, but these must have been completed at least 4 weeks prior to randomization.
3. Patients must not have an active infection requiring current treatment with parenteral antibiotics.
4. 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.
5. Patients should be carefully screened for depression at baseline and if there are indications or a history of depression it is strongly recommended that these patients be closely followed together with behavioral health or psychiatric medical support. Patients with an established diagnosis of depression that, in the assessment of the investigator may make the administration of IFNa or ipilimumab hazardous, should not be enrolled on this protocol. The risks and benefits of being treated with standard adjuvant IFNa should be weighed very carefully in consultation with behavioral health or psychiatry.
6. Patients must not have a documented history of inflammatory bowel disease (including ulcerative colitis and Crohn’s disease) or diverticulitis (history of diverticulosis is allowed).
7. Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), 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’s 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.
8. Due to the possible effect of treatment with ipilimumab on the immunologic response to infectious disease vaccines, patients
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method