Ignite Creation Date:
2025-12-25 @ 1:43 AM
Ignite Modification Date:
2025-12-26 @ 1:20 AM
Study NCT ID:
NCT05154994
Status:
RECRUITING
Last Update Posted:
2025-11-21
First Post:
2021-11-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Tremelimumab + Durvalumab(MEDI4736)+ Belinostat in Urothelial Carcinoma
Sponsor:
University of Utah
Organization:
Study Overview
Official Title:
RESOLVE : A Phase I Trial of Tremelimumab + Durvalumab(MEDI4736)+ Belinostat in Urothelial Carcinoma
Status:
RECRUITING
Status Verified Date:
2025-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RESOLVE
Brief Summary:
This phase I trial studies the side effects and best dose of belinostat when given together with durvalumab in treating patients with urothelial cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable) and has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Belinostat is a potential anti-cancer drug, known as a histone deacetylase (HDAC) inhibitor, which means that belinostat stops the activity of HDAC enzymes (an enzyme is a protein that in small amounts can speed up a biological reaction). HDAC enzymes play an important role in cell growth and cell death. Giving durvalumab and belinostat may improve the body's ability to fight cancer.
Detailed Description:
PRIMARY OBJECTIVES:
I. To assess the recommended phase 2 dose of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab alone in advanced urothelial carcinoma. (Phase 1A) II. To assess the ongoing safety of belinostat in combination with durvalumab in patients with advanced urothelial carcinoma. (Phase 1B)
SECONDARY OBJECTIVES:
I. To assess the efficacy of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab in patients with advanced urothelial carcinoma.
EXPLORATORY OBJECTIVES:
I. To assess the mechanism of action of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab.
II. To explore possible mechanisms of treatment resistance. III. Determine the feasibility of establishing patient-derived xenografts from tumor cells collected from enrolled subjects at baseline, and progression to better explore mechanisms of response and resistance. IIII. To explore possible biomarkers predictive of treatment benefit.
OUTLINE: This is a dose-escalation study of belinostat.
Patients receive durvalumab intravenously (IV) over 30 minutes on day 1. Patients also receive tremelimumab IV over 60 minutes on day 1 of cycle 1. Beginning cycle 2, patients receive belinostat IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
I. To assess the recommended phase 2 dose of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab alone in advanced urothelial carcinoma. (Phase 1A) II. To assess the ongoing safety of belinostat in combination with durvalumab in patients with advanced urothelial carcinoma. (Phase 1B)
SECONDARY OBJECTIVES:
I. To assess the efficacy of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab in patients with advanced urothelial carcinoma.
EXPLORATORY OBJECTIVES:
I. To assess the mechanism of action of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab.
II. To explore possible mechanisms of treatment resistance. III. Determine the feasibility of establishing patient-derived xenografts from tumor cells collected from enrolled subjects at baseline, and progression to better explore mechanisms of response and resistance. IIII. To explore possible biomarkers predictive of treatment benefit.
OUTLINE: This is a dose-escalation study of belinostat.
Patients receive durvalumab intravenously (IV) over 30 minutes on day 1. Patients also receive tremelimumab IV over 60 minutes on day 1 of cycle 1. Beginning cycle 2, patients receive belinostat IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2021-12484 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| HCI143952 | OTHER | Huntsman Cancer Institute/University of Utah | View | |
| P30CA042014 | NIH | None | https://reporter.nih.gov/quic… | View |