Time-of-Day Specified Immunotherapy for Advanced Melanoma, The TIME Trial
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Biopsy Procedure, Biospecimen Collection, Computed Tomography, Ipilimumab.
- Who it may be relevant to
- Registry conditions: Advanced Acral Melanoma, Advanced Cutaneous Melanoma, Advanced Mucosal Melanoma, Clinical Stage IV Cutaneous Melanoma AJCC v8. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
The TIME Trial - Phase II Randomized Controlled Trial of Time-of-Day Specified Immunotherapy for Advanced Melanoma
Overview
This phase II trial tests the safety and effectiveness of giving ipilimumab and nivolumab in the morning compared to other times of day in treating patients with melanoma that is stage IV or that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. While some patients have impressive outcomes with both of these drugs, over 40% of patients do not experience any clinical benefit. Studies have shown that the time of day that vaccines and other therapies are given have had an impact on response and survival. It is not known, however, whether time of day has an impact on response to immune checkpoint inhibitors, such as ipilimumab and nivolumab. Giving ipilimumab and nivolumab earlier in the day compared to later in the day may improve response to treatment and survival in patients with stage IV or unresectable melanoma.
Detailed description
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.
Interventions
- Procedure Biopsy Procedure
Undergo tumor tissue biopsy - Procedure Biospecimen Collection
Undergo check swab and blood sample collection - Procedure Computed Tomography
Undergo CT - Biological Ipilimumab
Given IV - Procedure Magnetic Resonance Imaging
Undergo MRI - Other Medical Device Usage and Evaluation
Wear an actigraphy device - Biological Nivolumab
Given IV - Other Questionnaire Administration
Ancillary studies
Primary outcome measures
- Progression-Free Survival (PFS) A versus (vs.) C and B vs. C [Time frame: From randomization to progression or death, assessed up to 5 years]
Secondary outcome measures (6)
- Incidence of Treatment-Related Adverse Events (AE) [Time frame: Up to 100 days after last dose of study treatment]
- Objective Response Rate (ORR) [Time frame: Up to 3 months]
- Overall Survival (OS) [Time frame: From randomization to death from any cause, assessed up to 5 years]
- PFS A vs. B [Time frame: From randomization to progression or death, assessed up to 5 years]
- Disease Specific Survival [Time frame: Up to 5 years]
- Rate of Receiving all Immunotherapy Doses as Scheduled [Time frame: Up to 4 cycles (cycle length = 3 weeks)]
Eligibility criteria
Inclusion criteria
- Pathologically confirmed American Joint Committee on Cancer (AJCC) 8th edition stage IV unresectable cutaneous, acral, or mucosal melanoma
- No uveal melanoma
- Patients with asymptomatic, non-hemorrhagic brain metastases < 2 cm are eligible
- No prior immunotherapy within 1 year, (serine/threonine-protein kinase B-raf \[BRAF\]/mitogen-activated protein kinase \[MEK\] inhibitors allowed)
- Eastern Cooperative Oncology Group (ECOG) 0-1
- Age ≥ 18
- Adequate organ function to receive ipilimumab/nivolumab
Exclusion criteria
- Immunosuppression (> 10mg prednisone daily)
- Active autoimmune disease that would preclude the administration of immunotherapy
- Active leptomeningeal disease
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 2 centers
- Emory University Hospital/Winship Cancer Institute — Atlanta
- Emory Saint Joseph's Hospital — Atlanta
Identifiers
NCT: NCT07155317 · STUDY00008806 · NCI-2025-03025 · STUDY00008806 · WINSHIP6451-24 · P30CA138292