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

Carcinoma, Squamous Cell of Head and Neck Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01836029
• Other study ID #: VRXP-A202
• Status: Completed
• Phase: Phase 2
• Start date: October 14, 2013
• Est. completion date: September 19, 2016

Study information

• Verified date: October 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: September 19, 2016
• Est. primary completion date: April 13, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Carcinoma, Squamous Cell of Head and Neck
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• VTX-2337
TLR8 Agonist
• Carboplatin

• Cisplatin

• 5-fluorouracil

• Placebo

Locations

Country	Name	City	State
United States	Northeast Georgia Cancer Care, LLC	Athens	Georgia
United States	Winship Cancer Institute	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	The Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Baltimore	Maryland
United States	Saint Charles Medical Center	Bend	Oregon
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Tower Hematology Oncology Medical Group	Beverly Hills	California
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Saint Louis Cancer Care, LLP	Bridgeton	Missouri
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Hollings Cancer Center	Charleston	South Carolina
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	VA Eastern Colorado Healthcare System	Denver	Colorado
United States	Oncology and Hematology Specialists, P.A.	Denville	New Jersey
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Saint Lukes Cancer Centre	Easton	Pennsylvania
United States	California Cancer Associates for Research and Excellence (CCARE)	Escondido	California
United States	Virginia Cancer Specialists, PD	Fairfax	Virginia
United States	San Antonio Military Medical Center	Fort Sam Houston	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Pennsylvania State Hershey Cancer Institute	Hershey	Pennsylvania
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	Monter Cancer Center	Lake Success	New York
United States	Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	University of California Norris Comprehensive Cancer Center	Los Angeles	California
United States	Crescent City Research Consortium, LLC	Marrero	Louisiana
United States	The West Clinic	Memphis	Tennessee
United States	Robert W. Veith, MD, LLC	Metairie	Louisiana
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Mount Sinai Medical Center	New York	New York
United States	The Bellevue Hospital	New York	New York
United States	Helen F. Graham Cancer Center	Newark	Delaware
United States	MD Anderson Cancer Center	Orlando	Florida
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Providence Cancer Center	Portland	Oregon
United States	Barnes Jewish Hospital	Saint Louis	Missouri
United States	Maine Center for Cancer Medicine	Scarborough	Maine
United States	Providence Cancer Institute	Southfield	Michigan
United States	Medical Oncology Associates, PS	Spokane	Washington
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Carle Cancer Center	Urbana	Illinois
United States	Aurora Advanced Healthcare, Inc.	Wauwatosa	Wisconsin
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Progression Free Survival (PFS) Between Treatment Groups Using irRECIST and Evaluated by Independent Radiology.	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	Comparison of Adverse Events (AEs) Between the Two Treatment Groups.	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.
Secondary	Comparison of Overall Survival (OS) Between the 2 Treatment Groups.	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.
Secondary	Comparison of the Objective Response Rate Between the Two Treatment Groups p	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.