Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Tavokinogene Telseplasmid With Electroporation, Pembrolizumab, and Epacadostat in Treating Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03823131
Recruitment Status : Not yet recruiting
First Posted : January 30, 2019
Last Update Posted : January 30, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Chase Heaton, MD, University of California, San Francisco

Brief Summary:
This phase II trial studies how well tavokinogene telseplasmid with electroporation, pembrolizumab, and epacadostat work in treating patients with squamous cell carcinoma of the head and neck that cannot be removed by surgery. Tavokinogene telseplasmid with electroporation is a gene therapy that may delay of tumor growth and which may have less toxicity than other methods of gene delivery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving tavokinogene telseplasmid with electroporation, pembrolizumab, and epacadostat may work better in treating squamous cell carcinoma of the head and neck.

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

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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).

EXPLORATORY OBJECTIVES:

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.

OUTLINE:

Patients receive tavokinogene telseplasmid intratumorally (IT) and undergo electroporation on days 1, 5 and 8. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on days 1 and 22, and epacadostat orally (PO) twice daily (BID). Treatment repeats every 42 days (6 weeks) for up to 9 courses or 12 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 36 months or 30 days after disease progression.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Trifecta Study: Optimizinging Antitumor Immunity Using Tavokinogene Telseplasmid With Electroporation, Pembrolizumab, and Epacadostat in Squamous Cell Carcinoma of the Head and Neck
Estimated Study Start Date : February 1, 2019
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : January 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (tavo-EP, pembrolizumab, epacadostat)
Patients receive tavokinogene telseplasmid IT and undergo electroporation on days 1, 5 and 8. Patients also receive pembrolizumab IV over 30 minutes on days 1 and 22, and epacadostat PO BID. Treatment repeats every 42 days (6 weeks) for up to 9 courses or 12 months in the absence of disease progression or unacceptable toxicity.
Device: Electroporation
Intratumoral
Other Names:
  • Electroporation of Tavokinogene Telseplasmid
  • electroporation therapy
  • EPT

Drug: Epacadostat
Given PO
Other Names:
  • INCB 024360
  • INCB024360

Drug: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  1. Best overall response rate by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 36 months ]
    The best overall response(BOR) 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).


Secondary Outcome Measures :
  1. Incidence of adverse events (AEs) by Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 36 months ]
    AEs will be graded and reported descriptively.

  2. Progression free survival (PFS) [ Time Frame: From enrollment to progression or last assessment, assessed up to 36 months ]
    PFS is defined as the number of days from enrollment to progression (for subjects who have progression) and the number of days from enrollment to last assessment (for subjects who do not have progression).

  3. Overall survival (OS) [ Time Frame: From enrollment to death, or date last known alive, assessed up to 36 months ]
    OS is defined as the number of days from enrollment to death, or from enrollment to date last known alive.

  4. Time to progression [ Time Frame: Up to 36 months ]
    Will be summarized using the Kaplan-Meier method.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy of at least 4 months
  • Patients must have histological or cytological diagnosis of carcinoma of the head and neck that is not amenable to surgical resection or locoregional radiation therapy with curative intent
  • At least one tumor accessible lesion (AL) for intratumoral injection and EP on investigator?s assessment meeting all criteria. An AL is defined as meeting the following criteria; (1) at least 0.3 cm x 0.3 cm in longest perpendicular diameters, (2) in a suitable location for application of electroporation. If the biopsied lesions were previously irradiated, they must demonstrate either radiographic or pathological evidence of recurrent or residual disease; Tumors invading the carotid artery or at other sites that the investigator believes to be at high risk of life-threatening hemorrhage should not be injected and these lesions may not be used to meet the inclusion criterion for injectable lesions
  • If patient has known brain metastases, they must have stable neurologic status following local therapy (surgery or radiation) for at least 4 weeks without the use of steroids or on stable or decreasing dose of =< 10 mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs) (patients with a history of carcinomatous meningitis are not eligible)
  • Patients may have had prior chemotherapy or immunotherapy or radiation therapy. Any drug related adverse events identified during prior therapy must be well controlled (typically resolution to =< grade 1, OR resolved upon investigator review prior to initiation of this therapy
  • No systemic antineoplastic therapy may be received by the patient between the time of the biopsy and the first administration of study treatment
  • Patient must agree to any protocol mandated biopsies of tumor (deemed accessible and safe for biopsy by the investigator?s assessment) and they must allow acquired tissue to be used for biomarker analysis
  • For women of childbearing potential, negative serum or urine pregnancy test within 14 days to the first epacadostat, pembrolizumab, or tavo-EP administration, and use of birth control from 30 days prior to the first epacadostat, pembrolizumab, or tavo-EP administration and 120 days following last day of epacadostat, pembrolizumab, or tavo-EP administration
  • Male patients must be surgically sterile, or must agree to use contraception during the study and at least 120 days following the last day of epacadostat, pembrolizumab, or tavo-EP administration

Exclusion Criteria:

  • Active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
  • Congestive heart failure (New York Heart Association class III to IV)
  • History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening corrected QT (QTc) interval > 480 milliseconds is excluded. In the event that a single QTc is > 480 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 480 milliseconds. For subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the corrected JT (JTc) interval may be used in place of the QTc with sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left bundle branch block are excluded
  • Uncontrolled or clinically significant conduction abnormalities (e.g., ventricular tachycardia on anti-arrhythmics are excluded), 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block (LAFB)/right bundle branch block (RBBB) are eligible
  • Uncontrolled, symptomatic ischemia within 6 months of first dose of study treatment or known myocardial infarction in the previous six months
  • Patients with electronic pacemakers or defibrillators
  • Evidence of interstitial lung disease or active, noninfectious pneumonitis including symptomatic and/or pneumonitis requiring treatment
  • Any other current or previous malignancy within the past 2 years that, in the opinion of the principal investigator will interfere with study-specific endpoints
  • Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) requiring systemic therapy at time of study enrollment
  • Hepatitis B ? Most nasopharyngeal cancer (NPC) patients have been infected with hepatitis B (Cancer Epidemol Biomarkers Prev. 2015. 24:1766-73, N = 711) and, therefore, the inclusion of healthy patients with a history of hepatitis B is a central part of this study. In addition, PD-1 antibodies have been proven to be safe in patients with active hepatitis and hepatocellular carcinoma (e.g. KEYNOTE 224). However, patients with hepatitis B virus (HBV) surface antigen positive (HBSAg) must have aspartate aminotransferase (AST) and total bilirubin < 1.5 x upper limit of normal (ULN) AND
  • Negative HBV ribonucleic acid (RNA) polymerase chain reaction (PCR) OR
  • On antivirals for HBV AND at least 8 weeks of prior anti-PD1 antibody therapy AND no history of AST or total bilirubin levels > 1.5 x ULN due to PD-1 antibody therapy
  • Hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is detected)
  • Presence of a gastrointestinal condition that may affect drug absorption. Administration of epacadostat through a feeding tube is permitted
  • Patients receiving systemic steroid therapy for a chronic inflammatory condition. Topical steroids, nasal and inhaled steroids are permitted. Prednisone or equivalent =< 10 mg/day is permitted as hormone replacement; higher dosage prednisone should be stopped at least 14 days prior to course 1 day 1 (C1D1)
  • Receipt of live attenuated vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
  • Subjects receiving monoamine oxidase inhibitors (MAOIs) or drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening
  • Any history of serotonin syndrome (SS) after receiving serotonergic drugs
  • Use of any UGT1A9 inhibitor from screening through follow-up period, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
  • Known allergy or reaction to any component of epacadostat, pembrolizumab, or tavo-EP formulation
  • Absolute neutrophil count (ANC) < 1.0 x 10^9/L
  • Platelets < 75 x 10^9/L
  • Hemoglobin < 9 g/dL or < 5.6 mmol/L (transfusion is acceptable to meet this criterion)
  • Serum creatinine >= 1.5 x institutional upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance [CrCl]) < 50 mL/min for subjects with creatinine levels > 1.5 x institutional ULN
  • AST or alanine aminotransferase (ALT) > 2.5 x institutional ULN
  • Alkaline phosphatase > 2.5 x ULN. Note: Subjects with 1) bone metastases and gamma-glutamyl transpeptidase (GGT) < 2.5 x ULN may enroll if the alkaline phosphatase is < 5 x ULN
  • Total bilirubin above 1.5 x the institutional ULN AND conjugated bilirubin >= 2.0 x ULN
  • International normalized ratio (INR) or prothrombin time (PT) > 1.5 x ULN
  • Activated partial thromboplastin time (aPTT) > 1.5 x ULN

Information from the National Library of Medicine

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


Locations
Layout table for location information
United States, California
UCSF Medical Center-Mount Zion Not yet recruiting
San Francisco, California, United States, 94115
Contact: Chase M. Heaton    415-502-1889    chase.heaton@ucsf.edu   
Principal Investigator: Chase M. Heaton         
Sponsors and Collaborators
University of California, San Francisco
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Chase Heaton UCSF Medical Center-Mount Zion

Layout table for additonal information
Responsible Party: Chase Heaton, MD, Asst Clinical Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03823131     History of Changes
Other Study ID Numbers: 172021
NCI-2018-02901 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17-24044
172021 ( Other Identifier: UCSF Medical Center-Mount Zion )
P30CA082103 ( U.S. NIH Grant/Contract )
First Posted: January 30, 2019    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents