A Randomized Phase 2 Trial of Ipilumumab and Nivolumab With or Without Hypofractionated Radiotherapy in Patients With Metastatic Melanoma
The main purpose of this study is to determine the safety of combining ipilimumab and nivolumab with hypofractionated radiotherapy to a single tumor in patients with metastatic melanoma. Another purpose of this study is to determine the effect of ipilimumab, nivolumab and hypofractionated radiotherapy on the cancer as compared to ipilimumab and nivolumab.
• Histologically confirmed metastatic melanoma.
• Have at least two measurable lesions (including the index lesion) according to RECIST (Response Evaluation Criteria in Solid Tumours)guidelines v1.1.
• Have an index lesion measuring between 1cm - 7cm that is amenable to hypofractionated radiation therapy (HFRT) at the discretion of the treating radiation oncologist
• Able to tolerate HFRT (e.g. lie flat and hold position for treatment)
• Able to provide signed, written informed consent and age \> 18 years at time of signing
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Recovery from the adverse effects of prior cancer treatments, defined as effects having resolved to NCI CTCAE v5 Grade 1 or better with the exception of alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by nivolumab and ipilimumab may be included (eg, hearing loss, neuropathy) upon approval of the Principal Investigator (PI).
• Female subjects of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for two weeks before the time of the first dose of study medication, while on study, through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Non-sterilized male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Acceptable forms of birth control include condoms, diaphragms, cervical cap, an intra-uterine device (IUD), surgical sterility (tubal ligation or a partner that has undergone a vasectomy), or oral contraceptives, OR the subject must agree to completely abstain from heterosexual intercourse. Abstinence at certain times of the cycle only, such as during the days of ovulation, after ovulation and withdrawal are not acceptable methods of birth control.
• Demonstrate adequate organ function; all screening labs should be performed within 21 days of date of consent.
• White blood cell \>= 2,500 cells/ul
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets \>=100,000 / mcL
• Hemoglobin \>=9 g/dL
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) \<=1.5 X upper limit of normal (ULN) OR \>=60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (Creatinine clearance should be calculated per institutional standard.)
• Serum total bilirubin \<= 1.5 X ULN OR
• Direct bilirubin \<= ULN for subjects with total bilirubin levels \> 1.5 ULN
• AST (SGOT) and ALT (SGPT) \<= 2.5 X ULN OR \<= 5 X ULN for subjects with liver metastases