The TIME Trial - Phase II Randomized Controlled Trial of Time-of-Day Specified Immunotherapy for Advanced Melanoma
Emory University
Summary
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.
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…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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)…
Interventions
- ProcedureBiopsy Procedure
Undergo tumor tissue biopsy
- ProcedureBiospecimen Collection
Undergo check swab and blood sample collection
- ProcedureComputed Tomography
Undergo CT
- BiologicalIpilimumab
Given IV
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- OtherMedical Device Usage and Evaluation
Wear an actigraphy device
- BiologicalNivolumab
Locations (2)
- Emory University Hospital/Winship Cancer InstituteAtlanta, Georgia
- Emory Saint Joseph's HospitalAtlanta, Georgia