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Chemotherapy Plus Cetuximab in Combination With VTX-2337 in Patients With Recurrent or Metastatic 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01836029
Recruitment Status : Completed
First Posted : April 19, 2013
Results First Posted : October 29, 2019
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Squamous Cell of Head and Neck Drug: VTX-2337 Drug: Carboplatin Drug: Cisplatin Drug: 5-fluorouracil Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 195 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 14, 2013
Actual Primary Completion Date : April 13, 2016
Actual Study Completion Date : September 19, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

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: VTX-2337
TLR8 Agonist

Drug: Carboplatin
Other Name: paraplatin

Drug: Cisplatin
Other Name: Platin

Drug: 5-fluorouracil
Other Names:
  • 5-FU
  • Efudex
  • Fluorouracil

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: Carboplatin
Other Name: paraplatin

Drug: Cisplatin
Other Name: Platin

Drug: 5-fluorouracil
Other Names:
  • 5-FU
  • Efudex
  • Fluorouracil

Drug: Placebo



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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..



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.


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

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

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): NCT01836029


Locations
Show Show 53 study locations
Sponsors and Collaborators
Celgene
Investigators
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Study Chair: Ezra Cohen, MD University of Chicago
Study Chair: Robert Ferris, MD, PhD University of Pittsburgh
Study Director: Amar Patel, MD Celgene

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01836029    
Other Study ID Numbers: VRXP-A202
First Posted: April 19, 2013    Key Record Dates
Results First Posted: October 29, 2019
Last Update Posted: October 29, 2019
Last Verified: October 2019
Keywords provided by Celgene:
SCCHN
HNSCC
Additional relevant MeSH terms:
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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
Cisplatin
Carboplatin
Fluorouracil
Cetuximab
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological