Ignite Creation Date:
2024-05-06 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 2:20 PM
Study NCT ID:
NCT05154994
Status:
SUSPENDED
Last Update Posted:
2024-06-18
First Post:
2021-11-30
Brief Title:
Tremelimumab DurvalumabMEDI4736 Belinostat in ARID1A Mutated Cancer Focus on Urothelial Carcinoma
Sponsor:
University of Utah
Organization:
University of Utah
Study Overview
Official Title:
RESOLVE A Phase I Trial of Tremelimumab DurvalumabMEDI4736 Belinostat in ARID1A Mutated Cancers With Focus on Urothelial Carcinoma
Status:
SUSPENDED
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Pending approval of cohort expansion
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 bodys 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 bodys 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 solid tumors harboring ARID1A mutations with focus on urothelial carcinoma Phase 1A II To assess the ongoing safety of belinostat in combination with durvalumab in patients with advanced solid tumors with ARID1A mutation with focus on urothelial cancer 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 cancer with ARID1A mutation
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 solid tumors harboring ARID1A mutations with focus on urothelial carcinoma Phase 1A II To assess the ongoing safety of belinostat in combination with durvalumab in patients with advanced solid tumors with ARID1A mutation with focus on urothelial cancer 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 cancer with ARID1A mutation
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:
None
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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P30CA042014 | NIH | Huntsman Cancer InstituteUniversity of Utah | httpsreporternihgovquickSearchP30CA042014 |
| NCI-2021-12484 | REGISTRY | None | None |
| HCI143952 | OTHER | None | None |