Condition or disease | Intervention/treatment | Phase |
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Stage III Cutaneous Melanoma Stage IV Cutaneous Melanoma Locally Advanced Melanoma Locally Advanced Solid Neoplasm Metastatic Head and Neck Squamous Cell Carcinoma Metastatic Malignant Solid Neoplasm Metastatic Melanoma Metastatic Urothelial Carcinoma Non-Small Cell Lung Carcinoma Stage IB Lung Cancer AJCC v7 Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8 Stage III Lung Cancer AJCC v8 Stage III Ureter Cancer AJCC v8 Stage IIIA Lung Cancer AJCC v8 Stage IIIB Lung Cancer AJCC v8 Stage IIIC Lung Cancer AJCC v8 Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IV Ureter Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 | Drug: Abexinostat Biological: Pembrolizumab | Phase 1 |
PRIMARY OBJECTIVES:
I. To determine the maximally tolerated and recommended phase 2 dose of abexinostat in combination with anti-PD-1/PD-L1 checkpoint inhibitor (CPI). (Dose escalation)
II. To determine the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients treated with abexinostat in combination with CPI in patients with prior primary (cohort A) or acquired (cohort B) resistance to prior CPI treatment. (Dose expansion)
SECONDARY OBJECTIVES:
I. To determine the objective response rate and median duration of response (DoR) by immune modified (i)RECIST criteria.
II. To determine the median progression-free survival (PFS).
III. To further characterize the safety profile of the treatment combination.
OUTLINE: This is a dose-escalation study of abexinostat.
Participants receive abexinostat orally (PO) twice daily (BID) on days 1-21 and pembrolizumab intravenously (IV) on over 30 minutes day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up for 90 days.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 42 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies |
Actual Study Start Date : | August 20, 2018 |
Estimated Primary Completion Date : | February 15, 2022 |
Estimated Study Completion Date : | April 15, 2022 |
Arm | Intervention/treatment |
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Experimental: Treatment (abexinostat, pembrolizumab)
Participants receive abexinostat PO BID on days 1-21 and pembrolizumab IV on over 30 minutes day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
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Drug: Abexinostat
Dose Level -1: 20 mg/m2 PO BID days 1-4, 8-11 of every 21 day cycle
Biological: Pembrolizumab 200 mg IV on day 1 of every 21 day cycle
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Has histologically confirmed locally advanced or metastatic solid tumor malignancy with one of the following tumor types:
Dose Expansion only:
Disease progression during or within 3 months of last dose of most recent line of prior antiPD-1/PD-L1-based treatment with a pattern of progression as defined as one of the following:
A tumor biopsy is mandatory unless
Has adequate baseline organ function, as demonstrated by the following:
Exclusion Criteria:
Has clinically significant cardiovascular disease including, but not limited to:
Has a history of untreated brain, or leptomeningeal, metastases (central nervous system (CNS) imaging is not required before study entry unless there is a clinical suspicion of CNS involvement). Subjects with previously treated brain metastases may participate provided:
This exception does not include leptomeningeal metastases, which is excluded regardless of clinical stability.
Has uncontrolled intercurrent illness including, but not limited to:
Contact: Claire Hooker | (415) 353-7084 | Claire.Hooker@ucsf.edu |
United States, California | |
University of California, San Francisco | Recruiting |
San Francisco, California, United States, 94143 | |
Contact: Claire Hooker 415-353-7084 Claire.Hooker@ucsf.edu | |
Contact 877-827-3222 cancertrials@ucsf.edu | |
Principal Investigator: Rahul Aggarwal, MD |
Principal Investigator: | Rahul Aggarwal, MD | University of California, San Francisco |
Tracking Information | |||||
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First Submitted Date ICMJE | July 5, 2018 | ||||
First Posted Date ICMJE | July 18, 2018 | ||||
Last Update Posted Date | May 28, 2021 | ||||
Actual Study Start Date ICMJE | August 20, 2018 | ||||
Estimated Primary Completion Date | February 15, 2022 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies | ||||
Official Title ICMJE | A Phase 1b Dose Escalation/Expansion Study of Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies | ||||
Brief Summary | This phase I trial studies the best dose and side effects of abexinostat and how well it works with given together with pembrolizumab in treating participants with microsatellite instability (MSI) solid tumors that have spread to other places in the body. Abexinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving abexinostat and pembrolizumab may work better in treating participants with solid tumors. | ||||
Detailed Description |
PRIMARY OBJECTIVES: I. To determine the maximally tolerated and recommended phase 2 dose of abexinostat in combination with anti-PD-1/PD-L1 checkpoint inhibitor (CPI). (Dose escalation) II. To determine the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients treated with abexinostat in combination with CPI in patients with prior primary (cohort A) or acquired (cohort B) resistance to prior CPI treatment. (Dose expansion) SECONDARY OBJECTIVES: I. To determine the objective response rate and median duration of response (DoR) by immune modified (i)RECIST criteria. II. To determine the median progression-free survival (PFS). III. To further characterize the safety profile of the treatment combination. OUTLINE: This is a dose-escalation study of abexinostat. Participants receive abexinostat orally (PO) twice daily (BID) on days 1-21 and pembrolizumab intravenously (IV) on over 30 minutes day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up for 90 days. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (abexinostat, pembrolizumab)
Participants receive abexinostat PO BID on days 1-21 and pembrolizumab IV on over 30 minutes day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions:
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
42 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | April 15, 2022 | ||||
Estimated Primary Completion Date | February 15, 2022 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
This exception does not include leptomeningeal metastases, which is excluded regardless of clinical stability.
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03590054 | ||||
Other Study ID Numbers ICMJE | 18956 NCI-2018-01395 ( Registry Identifier: Clinical Trials Reporting Program (CTRP) ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Rahul Aggarwal, University of California, San Francisco | ||||
Study Sponsor ICMJE | Rahul Aggarwal | ||||
Collaborators ICMJE | Xynomic Pharmaceuticals, Inc. | ||||
Investigators ICMJE |
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PRS Account | University of California, San Francisco | ||||
Verification Date | May 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |