Tavo With Electroporation, Pembrolizumab, and Epacadostat in Patients With Unresectable Head and Neck Cancer
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|ClinicalTrials.gov Identifier: NCT03823131|
Recruitment Status : Recruiting
First Posted : January 30, 2019
Last Update Posted : August 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Head and Neck Squamous Cell Carcinoma Recurrent Head and Neck Squamous Cell Carcinoma Unresectable Head and Neck Squamous Cell Carcinoma||Device: Electroporation Drug: Epacadostat Drug: Pembrolizumab||Phase 2|
I. Determine whether the combination of tavokinogene telseplasmid (tavo)-electroporation (EP), pembrolizumab, and epacadostat increases the best overall response rate (BORR) in squamous cell carcinoma of the head and neck (SCCHN) compared with historical data for pembrolizumab monotherapy.
I. Assess the safety of tavo-EP and pembrolizumab in combination with epacadostat (Common Terminology Criteria for Adverse Events [CTCAE] version 4).
II. Determine the durability of clinical benefits in patients treated with tavo-EP, pembrolizumab, and epacadostat as assessed by time to progression, median progression-free survival (PFS), median overall survival (OS).
I. Determine whether the combination of tavo-EP, pembrolizumab, and epacadostat increases the objective response rate in SCCHN compared with emerging data for pembrolizumab in combination with epacadostat.
II. Determine the effects of combination therapy on treated and untreated lesions by examining paired biopsy specimens for changes in inflammatory gene expression, relative proportion of effector versus regulatory T cells, evaluation of inflammatory cytokines, T-cell activation, clonality, and other hallmarks of immune activation.
III. Explore systemic markers of immune activation by examining circulating T-cell populations for changes in the frequency and effector function of short-lived effector cells and memory T cells.
IV. Explore changes in functional immune responses using enzyme-linked immunosorbent spot (Elispot) and other assays.
V. To explore biomarkers that inform scientific understanding of this therapeutic treatment through analysis of specimens retained for Future Biomedical Research.
This is a multi-center, open label, 2-stage, double-arm, clinical trial in which patients in Stage 1 will receive either tavo-EP with pembrolizumab, and epacadostat (Arm A) or tavo-EP and pembrolizumab (Arm B) after a dose escalation safety lead-in phase. Stage 2 will open pending additional clinical and translational data emerging from Stage 1.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||68 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Trifecta Study: Optimizing Antitumor Immunity Using Tavokinogene Telseplasmid With Electroporation, Pembrolizumab, and Epacadostat in Squamous Cell Carcinoma of the Head and Neck|
|Actual Study Start Date :||May 16, 2019|
|Estimated Primary Completion Date :||January 1, 2022|
|Estimated Study Completion Date :||January 1, 2024|
Experimental: Arm A: Tavo-EP, pembrolizumab, epacadostat
tavo-EP:pUMVC3-hIL-12-NGVL33 (tavo-EP) will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
Experimental: Arm B: Tavo-EP, pembrolizumab
tavo-EP:pUMVC3-hIL-12-NGVL33 (tavo-EP) will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks.
- Best Overall Response Rate [ Time Frame: Up to 36 months ]The best overall response (BORR) is the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurement recorded since the treatment started). The percentage of patients who attain a confirmed complete response (CR), or partial response (PR) over the trial with the triplet treatment with a 4-week confirmatory scan per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 will be reported and percentage calculated will be relative to all patients who received the study therapy, and 95% confidence interval is calculated by the Clopper-Pearson (exact binomial) method
- Incidence of treatment- related adverse events (AEs) [ Time Frame: Up to 36 months ]Treatment-related AEs will be graded and reported descriptively using by Common Terminology Criteria for Adverse Events version 4
- Progression free survival (PFS) [ Time Frame: From enrollment to progression or last assessment, assessed up to 36 months ]Progression free survival (PFS) is defined as the number of days from the date of enrollment to the date of progression or death regardless of cause. . Patients who do not have a documented progression or death will be censored on the date of last assessment
- Overall survival (OS) [ Time Frame: From enrollment to death, or date last known alive, assessed up to 36 months ]Overall survival (OS) is defined as the number of days from the date of enrollment to the date of death regardless of cause, patients without a death date will be censored on the date last known alive.
- Time to progression [ Time Frame: Up to 36 months ]Will be summarized using the Kaplan-Meier method.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03823131
|Contact: Madeleine Welshemail@example.com|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94115|
|Contact: Madeleine Welsh 877-827-3222 firstname.lastname@example.org|
|Principal Investigator: Chase M. Heaton, MD|
|Principal Investigator:||Chase Heaton, MD||University of California, San Francisco|