Clinical trial · Interventional
Time-of-Day Specified Immunotherapy for Advanced Melanoma, The TIME Trial
The TIME Trial - Phase II Randomized Controlled Trial of Time-of-Day Specified Immunotherapy for Advanced Melanoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (10)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced Acral Melanoma | Acral Melanoma | CURATED_BROADER | 0.78 |
| Advanced Cutaneous Melanoma | Cutaneous Melanoma | CURATED_BROADER | 0.78 |
| Advanced Mucosal Melanoma | Mucosal Melanoma | CURATED_BROADER | 0.78 |
| Clinical Stage IV Cutaneous Melanoma AJCC v8 | Melanoma | PROBABILISTIC | 0.70 |
| Metastatic Acral Melanoma | Acral Melanoma | CURATED_BROADER | 0.78 |
| Metastatic Cutaneous Melanoma | Cutaneous Melanoma | CURATED_BROADER | 0.78 |
| Metastatic Mucosal Melanoma | Mucosal Melanoma | CURATED_BROADER | 0.78 |
Interventions
Interventions (8)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Biopsy Procedure | Procedure | — | UNRESOLVED |
| Biospecimen Collection | Procedure | — | UNRESOLVED |
| Computed Tomography | Procedure | — | UNRESOLVED |
| Ipilimumab | Biological | Ipilimumab | ALIAS |
| Magnetic Resonance Imaging | Procedure | — | UNRESOLVED |
| Medical Device Usage and Evaluation | Other | — | UNRESOLVED |
| Nivolumab | Biological | Nivolumab | ALIAS |
| Questionnaire Administration | Other | — | UNRESOLVED |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- Arm I (nivolumab, ipilimumab)
- description
- Patients receive nivolumab 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, CT or MRI and MRI or CT of brain throughout the study. Additionally, patients may optionally undergo tumor tissue biopsy throughout the study.
- interventionNames
- Procedure: Biopsy Procedure
- Procedure: Biospecimen Collection
- Procedure: Computed Tomography
- Biological: Ipilimumab
- Procedure: Magnetic Resonance Imaging
- Other: Medical Device Usage and Evaluation
- Biological: Nivolumab
- Other: Questionnaire Administration
- type
- EXPERIMENTAL
- label
- Arm II (nivolumab, ipilimumab)
- description
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (0)
Data not yet available