Ipilimumab and Nivolumab in Treating Patients with Stage III-IV Melanoma That Cannot Be Removed by Surgery
- Histologic diagnosis of unresectable III or stage IV metastatic melanoma
- Subjects must have at least 1 extracranial, unresectable, non-bony lesion that is measurable radiographically (based on RECIST 1.1)
- No prior CTLA-4 or PD-1/PD-L1 therapy for the treatment of metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Life expectancy >= 4 months
- White blood cell (WBC) count >= 2000/uL
- Absolute neutrophil count (ANC) >= 1500/uL
- Platelets >= 100,000/uL
- Hemoglobin (Hgb) >= 9 g/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
- Total bilirubin =< 1.5 x ULN (< 3 mg/dL for subjects with Gilbert's disease)
- Serum creatinine =< 1.5 x ULN or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula)
- Females of childbearing potential who are sexually active with a non-sterilized male partner must use 2 methods of effective contraception from screening, and must agree to continue using such precautions for 23 weeks after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician; periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control; (females of childbearing potential are defined as those who are not surgically sterile [i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy] or postmenopausal ([defined as 12 months with no menses without an alternative medical cause]); non-sterilized males who are sexually active with a female partner of childbearing potential must use 2 acceptable methods of effective contraception from day 1 and for 31 weeks after receipt of the final dose of investigational product; acceptable methods of effective contraception are described in the following table: * Barrier methods: male condom plus spermicide, cap plus spermicide, or diaphragm plus spermicide * Intrauterine device methods: copper T, levonorgestrel-releasing intrauterine system (e.g. Mirena), also considered a hormonal method * Hormonal methods: implants, hormone shot or injection, combined pill, min ipilimumab ll, or patch
- Active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- History of motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre syndrome, myasthenia gravis)
- Other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator
- Known immunodeficiency or human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection; antibody to hepatitis B or C without evidence of active infection may be allowed
- History of severe allergic reactions to any unknown allergens or any components of the study drugs
- Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders)
- Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study
- Lack of availability for immunological and clinical assessments or post-study follow-up contact to determine relapse and survival
- Women who are breastfeeding or who are pregnant as evidenced by a positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) performed within 14 days of the first dose of study drug and by a urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours of the first dose of study drug(s)
- Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk
I. To estimate the objective response rate (complete response [CR], partial response [PR] as per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) at 12 weeks in patients with advanced melanoma who receive adaptive dosing of ipilimumab/nivolumab combination therapy.
I. To estimate the rate of favorable antitumor effect at week 6.
II. To estimate the objective response by RECIST 1.1 at week 6.
III. To estimate the response rate by immune-related RECIST (irRECIST) at week 12.
IV. To estimate the duration of response.
V. To determine the progression free survival as assessed by both RECIST and irRECIST.
VI. To assess toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0.
VII. To determine best overall response.
I. To examine the association of immunologic biomarkers with response.
II. To investigate the use of a novel positron emission tomography (PET) tracer to image the programmed cell death ligand-1 protein.
Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 2 doses. Patients that have achieved a favorable antitumor effect receive nivolumab IV over 30 minutes alone every 4 weeks for 2 doses in the absence of disease progression or unacceptable toxicity. Patients that do not achieve a favorable antitumor effect receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 2 additional doses. Patients that still do not achieve a favorable antitumor effect may receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for another 2 doses at the discretion of investigator.
After completion of study treatment, patients are followed up for 100 days, every 6 weeks until week 12, every 12 weeks during years 0-1, and then every 24 weeks during years 1-3.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Michael Andrew Postow
- Primary ID 17-162
- Secondary IDs NCI-2017-00899
- Clinicaltrials.gov ID NCT03122522