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

October 11, 2019 updated by: Celgene

A Randomized, Double-Blind, Placebo-Controlled Study of Chemotherapy Plus Cetuximab in Combination With VTX 2337 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

195

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Beverly Hills, California, United States, 90211
        • Tower Hematology Oncology Medical Group
      • Escondido, California, United States, 92025
        • California Cancer Associates for Research and Excellence (cCare)
      • La Jolla, California, United States, 92093
        • University of California San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90033
        • University of California Norris Comprehensive Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center
      • Denver, Colorado, United States, 80220
        • VA Eastern Colorado Healthcare System
    • Delaware
      • Newark, Delaware, United States, 19713
        • Helen F. Graham Cancer Center
    • Florida
      • Orlando, Florida, United States, 32806
        • MD Anderson Cancer Center
    • Georgia
      • Athens, Georgia, United States, 30607
        • Northeast Georgia Cancer Care, LLC
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute
    • Hawaii
      • Honolulu, Hawaii, United States, 96859
        • Tripler Army Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
    • Kansas
      • Westwood, Kansas, United States, 66205
        • University of Kansas Cancer Center
    • Louisiana
      • Marrero, Louisiana, United States, 70072
        • Crescent City Research Consortium, LLC
      • Metairie, Louisiana, United States, 70006-2936
        • Robert W. Veith, MD, LLC
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Center for Cancer Medicine
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
      • Bethesda, Maryland, United States, 20889
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
      • Southfield, Michigan, United States, 48075
        • Providence Cancer Institute
    • Missouri
      • Bridgeton, Missouri, United States, 63044
        • Saint Louis Cancer Care, LLP
      • Saint Louis, Missouri, United States, 63110
        • Barnes Jewish Hospital
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Nevada Cancer Research Foundation
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center
    • New Jersey
      • Denville, New Jersey, United States, 07834
        • Oncology and Hematology Specialists, P.A.
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • Lake Success, New York, United States, 11042
        • Monter Cancer Center
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • New York, New York, United States, 10016
        • The Bellevue Hospital
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
      • Winston-Salem, North Carolina, United States, 27103
        • Wake Forest University Baptist Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0502
        • University of Cincinnati
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland
    • Oregon
      • Bend, Oregon, United States, 97701
        • Saint Charles Medical Center
      • Portland, Oregon, United States, 97213
        • Providence Cancer Center
    • Pennsylvania
      • Easton, Pennsylvania, United States, 18045
        • Saint Lukes Cancer Centre
      • Hershey, Pennsylvania, United States, 17033
        • Pennsylvania State Hershey Cancer Institute
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Hollings Cancer Center
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • The West Clinic
    • Texas
      • Dallas, Texas, United States, 75390-8852
        • University of Texas Southwestern Medical Center at Dallas
      • Fort Sam Houston, Texas, United States, 78234
        • San Antonio Military Medical Center
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PD
    • Washington
      • Spokane, Washington, United States, 99208
        • Medical Oncology Associates, PS
      • Tacoma, Washington, United States, 98431
        • Madigan Army Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Wauwatosa, Wisconsin, United States, 53226
        • Aurora Advanced Healthcare, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Drug: Cisplatin
Other Names:
  • Platin
Drug: Carboplatin
Other Names:
  • paraplatin
Drug: 5-fluorouracil
Other Names:
  • 5-FU
  • Fluorouracil
  • Efudex
Drug: VTX-2337
TLR8 Agonist
ACTIVE_COMPARATOR: 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.
Drug: Placebo
Drug: Cisplatin
Other Names:
  • Platin
Drug: Carboplatin
Other Names:
  • paraplatin
Drug: 5-fluorouracil
Other Names:
  • 5-FU
  • Fluorouracil
  • Efudex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of Progression Free Survival (PFS) Between Treatment Groups Using irRECIST and Evaluated by Independent Radiology.
Time Frame: PFS is the time from randomization until disease progression or death, whichever comes first.
PFS was based on central assessment by a blinded independent radiologist per immune related response evaluation criteria for solid tumors (irRECIST) and was summarized and displayed by treatment arm using Kaplan-Meier methods. Treatments were compared using a stratified log-rank test controlling for randomization stratification factors. The hazard ratio between the 2 treatment arms, as well as the associated one-sided 90% CI and p-value, were presented using a Cox proportional hazards regression model.
PFS is the time from randomization until disease progression or death, whichever comes first.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of Adverse Events (AEs) Between the Two Treatment Groups.
Time Frame: AEs were collected from the first dose of study drug given on Cycle 1 Day 1 until 7 days after the dose of study drug or End of Treatment visit, whichever occurred first. Overall mean duration of exposure was 25.3 weeks.
The frequency and severity of adverse events, including any clinically significant changes in physical exam, laboratory values, or other clinical assessment.
AEs were collected from the first dose of study drug given on Cycle 1 Day 1 until 7 days after the dose of study drug or End of Treatment visit, whichever occurred first. Overall mean duration of exposure was 25.3 weeks.
Comparison of Overall Survival (OS) Between the 2 Treatment Groups.
Time Frame: OS is the time from randomization until death due to any cause or the date last confirmed to be alive.
Estimated using Kaplan-Meier product limit estimates, 1-sided stratified log-rank test, and Cox proportional hazard model; all with 90% 1-sided confidence intervals.
OS is the time from randomization until death due to any cause or the date last confirmed to be alive.
Comparison of the Objective Response Rate Between the Two Treatment Groups p
Time Frame: From the time of randomization until the best response on treatment is documented.
Objective response rate is defined as the percentage of subjects who achieve best overall response of irCR or irPR pr irRECIST and evaluated by independent radiology..
From the time of randomization until the best response on treatment is documented.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Investigators

  • Study Chair: Ezra Cohen, MD, University of Chicago
  • Study Chair: Robert Ferris, MD, PhD, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 14, 2013

Primary Completion (ACTUAL)

April 13, 2016

Study Completion (ACTUAL)

September 19, 2016

Study Registration Dates

First Submitted

April 12, 2013

First Submitted That Met QC Criteria

April 16, 2013

First Posted (ESTIMATE)

April 19, 2013

Study Record Updates

Last Update Posted (ACTUAL)

October 29, 2019

Last Update Submitted That Met QC Criteria

October 11, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VRXP-A202

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carcinoma, Squamous Cell of Head and Neck

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Saudi Arabia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe