PRIMARY OBJECTIVE:
I. To compare the progression-free survival (PFS) following administration of
immunotherapy at different time-of-day intervals for previously untreated unresectable or
metastatic melanoma.
SECONDARY OBJECTIVES:
I. To compare adverse events (AEs). II. Rate of receiving all immunotherapy doses as
scheduled. III. Objective response rate. IV. Melanoma specific survival (MSS) and overall
survival (OS). V. Patient-reported quality of life (QOL).
TERTIARY/EXPLORATORY OBJECTIVE:
I. To explore immune biomarkers associated with clinical efficacy (PFS, OS).
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I: Patients receive nivolumab intravenously (IV) over 60 minutes and ipilimumab IV
over 90 minutes at 0800-1100 on day 1 of each cycle. Cycles repeat every 3 weeks for 4
cycles in the absence of disease progression or unacceptable toxicity. Patients then
receive maintenance nivolumab for up to a total of 2 years. Patients wear an actigraphy
device for 5-7 days at enrollment prior to first infusion and for up to 4 weeks then over
3 weeks starting with visit 4. Patients also undergo check swab and blood sample
collection, computed tomography (CT) or magnetic resonance imaging (MRI) and MRI or CT of
brain throughout the study. Additionally, patients may optionally undergo tumor tissue
biopsy throughout the study.
ARM II: Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes
at 1100-1400 on day 1 of each cycle. Cycles repeat every 3 weeks for 4 cycles in the
absence of disease progression or unacceptable toxicity. Patients then receive
maintenance nivolumab for up to a total of 2 years. Patients wear an actigraphy device
for 5-7 days at enrollment prior to first infusion and for up to 4 weeks then over 3
weeks starting with visit 4. Patients also undergo check swab and blood sample
collection, CT or MRI and MRI or CT of brain throughout the study. Additionally, patients
may optionally undergo tumor tissue biopsy throughout the study.
ARM III: Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes
at 1400-1700 on day 1 of each cycle. Cycles repeat every 3 weeks for 4 cycles in the
absence of disease progression or unacceptable toxicity. Patients then receive
maintenance nivolumab for up to a total of 2 years. Patients wear an actigraphy device
for 5-7 days at enrollment prior to first infusion and for up to 4 weeks then over 3
weeks starting with visit 4. Patients also undergo check swab and blood sample
collection, CT or MRI and MRI or CT of brain throughout the study. Additionally, patients
may optionally undergo tumor tissue biopsy throughout the study.
After completion of study treatment, patients are followed up every 3 months for 12
months, then for up to year 5.
