Chemotherapy Plus Cetuximab in Combination With VTX-2337 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

NCT ID: NCT01836029

Last Updated: 2019-10-29

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

195 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-14

Study Completion Date

2016-09-19

Brief Summary

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The purpose of this study is to compare the progression-free survival of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with VTX-2337 + cisplatin or carboplatin + 5-FU + cetuximab versus patients treated with cisplatin or carboplatin + 5-FU + cetuximab alone (standard-of-care; SOC). Safety and overall survival will also be evaluated.

Detailed Description

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This is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of VTX 2337 in combination with cisplatin or carboplatin, 5-FU and cetuximab in prolonging the progression-free survival in subjects with recurrent or metastatic squamous cell carcinoma of the head and neck.

OBJECTIVES:

Primary Objective:

To compare the efficacy of VTX 2337 plus SOC to SOC alone in prolonging the PFS of patients with recurrent or metastatic SCCHN using irRECIST evaluated by independent radiology review.

Secondary Objectives:

To compare the following between the two treatment groups:

* Safety of VTX 2337 by adverse events, including clinically significant changes in physical examination, peripheral blood hematology, serum chemistry, urinalysis, and ECG.
* Efficacy of VTX 2337 plus SOC in prolonging the OS of patients with recurrent or metastatic SCCHN.
* Efficacy of VTX-2337 plus SOC on ORR, DOBR, DCR, and DDC by irRECIST and evaluation by independent radiology review.
* Efficacy of VTX-2337 plus SOC on ORR, DOBR, DCR, and DDC by RECIST v1.1 and evaluation by independent radiology review.
* Efficacy of VTX 2337 plus SOC to SOC alone in prolonging the PFS by RECIST v1.1 and evaluation by independent radiology review.
* Efficacy of VTX 2337 plus SOC to SOC alone in prolonging the PFS by irRECIST and evaluation by investigators.

Exploratory Objectives:

* To compare genetic polymorphisms that may impact the response of patients to a TLR8 agonist or to cetuximab between the two treatment groups.
* To compare immune biomarker response to VTX 2337 plus SOC as measured by a multiplexed panel of cytokines, chemokines, and inflammatory markers between the two treatment groups.
* To compare the effect of immune cell subsets within the tumor on response to VTX-2337 and/or clinical outcome, as measured by immunohistochemistry in primary tumor tissue between the two treatment groups.
* To assess the PK of VTX-2337.

OUTLINE:

Subjects will be screened for eligibility (within 14 days) and qualified subjects will be randomized 1:1 to 1 of 2 treatment groups: SOC + VTX 2337 or SOC + placebo.

Tumor assessments will be by CT or MRI starting at Week 12 (± 3 days), then at Week 18 (± 3 days) and every 8 weeks (± 7 days) thereafter. Response will be evaluated by immune-related RECIST criteria (irRECIST) and confirmed by an independent radiologist.

Upon independent confirmation of disease progression, active participation in the study is complete and subjects will undergo the End of Treatment evaluations.

Subjects will be followed for survival until \~12 months after the last subject is randomized.

Conditions

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Carcinoma, Squamous Cell of Head and Neck

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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chemotherapy and cetuximab plus VTX-2337

VTX-2337 (3.0 mg/m2) will be administered on Day 8 and Day 15 of a 21-day cycle for 6 cycles, followed by dosing on Days 8 and 22 of 28-day cycles until disease progression.

Cisplatin (100 mg/m2) OR carboplatin (AUC 5 mg/mL/min) will be administered on Day 1 of a 21-day cycle for a maximum of 6 cycles.

5-FU (1000 mg/m2) will be administered on Days 1-4 of a 21-day cycle for a maximum of 6 cycles.

Cetuximab (initial dose: 400 mg/m2; remaining doses: 250 mg/m2) will be administered weekly until disease progression.

Group Type EXPERIMENTAL

VTX-2337

Intervention Type DRUG

TLR8 Agonist

Carboplatin

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

5-fluorouracil

Intervention Type DRUG

chemotherapy and cetuximab plus placebo

Placebo (3.0 mg/m2) will be administered on Day 8 and Day 15 of a 21-day cycle for 6 cycles, followed by dosing on Days 8 and 22 of 28-day cycles until disease progression.

Cisplatin (100 mg/m2) OR carboplatin (AUC 5 mg/mL/min) will be administered on Day 1 of a 21-day cycle for a maximum of 6 cycles.

5-FU (1000 mg/m2) will be administered on Days 1-4 of a 21-day cycle for a maximum of 6 cycles.

Cetuximab (initial dose: 400 mg/m2; remaining doses: 250 mg/m2) will be administered weekly until disease progression.

Group Type ACTIVE_COMPARATOR

Carboplatin

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

5-fluorouracil

Intervention Type DRUG

Placebo

Intervention Type DRUG

Interventions

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VTX-2337

TLR8 Agonist

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

5-fluorouracil

Intervention Type DRUG

Placebo

Intervention Type DRUG

Other Intervention Names

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paraplatin Platin 5-FU Efudex Fluorouracil

Eligibility Criteria

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Inclusion Criteria

* Ability and willingness to provide written informed consent
* Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
* Locoregionally recurrent or metastatic disease that has not previously been treated with systemic therapy of recurrent or metastatic disease
* At least one measurable lesion on screening CT or MRI
* 18 years of age or older
* ECOG performance status of 0 or 1
* Acceptable bone marrow, renal, and hepatic function based upon screening lab tests
* Willingness to use medically acceptable contraception
* For females with reproductive potential: a negative serum pregnancy test

Exclusion Criteria

* Disease which is amenable to curative local therapy
* Nasopharyngeal, salivary gland, lip or sinonasal carcinoma
* Surgery or irradiation ≤ 4 weeks prior to randomization
* Prior systemic anti-cancer therapy, unless administered for localized SCCHN and completed at least 6 months prior to disease recurrence
* Treatment with an investigational agent ≤ 30 days prior to randomization
* Treatment with corticosteroids within 2 weeks
* A requirement for chronic systemic immunosuppressive therapy for any reason
* Prior serious infusion reaction to cetuximab
* Treatment with an immunotherapy within 30 days
* Known brain metastases, unless stable for at least 28 days
* Active autoimmune disease currently requiring therapy
* Known infection with HIV
* Significant cardiac disease within 6 months
* Pregnant or breast-feeding females
* History of another primary malignancy, with the exception of (i) curatively resected non-melanoma skin cancer, (ii) curatively treated in situ cervical cancer, or (iii) other malignancy curatively treated with no evidence of disease and no anticancer therapy administered for 3 years prior to randomization, with the exception of adjuvant hormonal therapy for breast cancer
* Other conditions or circumstances that could interfere with the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ezra Cohen, MD

Role: STUDY_CHAIR

University of Chicago

Robert Ferris, MD, PhD

Role: STUDY_CHAIR

University of Pittsburgh

Amar Patel, MD

Role: STUDY_DIRECTOR

Celgene

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Tower Hematology Oncology Medical Group

Beverly Hills, California, United States

Site Status

California Cancer Associates for Research and Excellence (CCARE)

Escondido, California, United States

Site Status

University of California San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

University of California Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status

VA Eastern Colorado Healthcare System

Denver, Colorado, United States

Site Status

Helen F. Graham Cancer Center

Newark, Delaware, United States

Site Status

MD Anderson Cancer Center

Orlando, Florida, United States

Site Status

Northeast Georgia Cancer Care, LLC

Athens, Georgia, United States

Site Status

Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Tripler Army Medical Center

Honolulu, Hawaii, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status

Crescent City Research Consortium, LLC

Marrero, Louisiana, United States

Site Status

Robert W. Veith, MD, LLC

Metairie, Louisiana, United States

Site Status

Maine Center for Cancer Medicine

Scarborough, Maine, United States

Site Status

The Sidney Kimmel Comprehensive Cancer Center at John Hopkins

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Providence Cancer Institute

Southfield, Michigan, United States

Site Status

Saint Louis Cancer Care, LLP

Bridgeton, Missouri, United States

Site Status

Barnes Jewish Hospital

St Louis, Missouri, United States

Site Status

Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Oncology and Hematology Specialists, P.A.

Denville, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Monter Cancer Center

Lake Success, New York, United States

Site Status

The Bellevue Hospital

New York, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

University Hospitals of Cleveland

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Saint Charles Medical Center

Bend, Oregon, United States

Site Status

Providence Cancer Center

Portland, Oregon, United States

Site Status

Saint Lukes Cancer Centre

Easton, Pennsylvania, United States

Site Status

Pennsylvania State Hershey Cancer Institute

Hershey, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Hollings Cancer Center

Charleston, South Carolina, United States

Site Status

The West Clinic

Memphis, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

San Antonio Military Medical Center

Fort Sam Houston, Texas, United States

Site Status

Virginia Cancer Specialists, PD

Fairfax, Virginia, United States

Site Status

Medical Oncology Associates, PS

Spokane, Washington, United States

Site Status

Madigan Army Medical Center

Tacoma, Washington, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Aurora Advanced Healthcare, Inc.

Wauwatosa, Wisconsin, United States

Site Status

Countries

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United States

References

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Ferris RL, Saba NF, Gitlitz BJ, Haddad R, Sukari A, Neupane P, Morris JC, Misiukiewicz K, Bauman JE, Fenton M, Jimeno A, Adkins DR, Schneider CJ, Sacco AG, Shirai K, Bowles DW, Gibson M, Nwizu T, Gottardo R, Manjarrez KL, Dietsch GN, Bryan JK, Hershberg RM, Cohen EEW. Effect of Adding Motolimod to Standard Combination Chemotherapy and Cetuximab Treatment of Patients With Squamous Cell Carcinoma of the Head and Neck: The Active8 Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):1583-1588. doi: 10.1001/jamaoncol.2018.1888.

Reference Type DERIVED
PMID: 29931076 (View on PubMed)

Chow LQM, Morishima C, Eaton KD, Baik CS, Goulart BH, Anderson LN, Manjarrez KL, Dietsch GN, Bryan JK, Hershberg RM, Disis ML, Martins RG. Phase Ib Trial of the Toll-like Receptor 8 Agonist, Motolimod (VTX-2337), Combined with Cetuximab in Patients with Recurrent or Metastatic SCCHN. Clin Cancer Res. 2017 May 15;23(10):2442-2450. doi: 10.1158/1078-0432.CCR-16-1934. Epub 2016 Nov 3.

Reference Type DERIVED
PMID: 27810904 (View on PubMed)

Northfelt DW, Ramanathan RK, Cohen PA, Von Hoff DD, Weiss GJ, Dietsch GN, Manjarrez KL, Randall TD, Hershberg RM. A phase I dose-finding study of the novel Toll-like receptor 8 agonist VTX-2337 in adult subjects with advanced solid tumors or lymphoma. Clin Cancer Res. 2014 Jul 15;20(14):3683-91. doi: 10.1158/1078-0432.CCR-14-0392. Epub 2014 May 7.

Reference Type DERIVED
PMID: 24807889 (View on PubMed)

Other Identifiers

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VRXP-A202

Identifier Type: -

Identifier Source: org_study_id

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