Clinical trial NCT01836029: Chemotherapy Plus Cetuximab in Combination With VTX-2337 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Squamous Cell of Head and Neck
Keywords: SCCHN
HNSCC
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2013-04-19
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Comparison of Progression Free Survival (PFS) Between Treatment Groups Using irRECIST and Evaluated by Independent Radiology.
timeFrame: PFS is the time from randomization until disease progression or death, whichever comes first.
Secondary outcomes:
measure: Comparison of Adverse Events (AEs) Between the Two Treatment Groups.
timeFrame: 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.
measure: Comparison of Overall Survival (OS) Between the 2 Treatment Groups.
timeFrame: OS is the time from randomization until death due to any cause or the date last confirmed to be alive.
measure: Comparison of the Objective Response Rate Between the Two Treatment Groups p
timeFrame: From the time of randomization until the best response on treatment is documented.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Beverly Hills
country: United States
facility: Tower Hematology Oncology Medical Group
state: California
city: Escondido
country: United States
facility: California Cancer Associates for Research and Excellence (CCARE)
state: California
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California Norris Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Denver
country: United States
facility: VA Eastern Colorado Healthcare System
state: Colorado
city: Newark
country: United States
facility: Helen F. Graham Cancer Center
state: Delaware
city: Orlando
country: United States
facility: MD Anderson Cancer Center
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care, LLC
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Honolulu
country: United States
facility: Tripler Army Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Marrero
country: United States
facility: Crescent City Research Consortium, LLC
state: Louisiana
city: Metairie
country: United States
facility: Robert W. Veith, MD, LLC
state: Louisiana
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine
state: Maine
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute
state: Michigan
city: Bridgeton
country: United States
facility: Saint Louis Cancer Care, LLP
state: Missouri
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Denville
country: United States
facility: Oncology and Hematology Specialists, P.A.
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Lake Success
country: United States
facility: Monter Cancer Center
state: New York
city: New York
country: United States
facility: The Bellevue Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Bend
country: United States
facility: Saint Charles Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center
state: Oregon
city: Easton
country: United States
facility: Saint Lukes Cancer Centre
state: Pennsylvania
city: Hershey
country: United States
facility: Pennsylvania State Hershey Cancer Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center
state: South Carolina
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Fort Sam Houston
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PD
state: Virginia
city: Spokane
country: United States
facility: Medical Oncology Associates, PS
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Wauwatosa
country: United States
facility: Aurora Advanced Healthcare, Inc.
state: Wisconsin
Study officials:
affiliation: University of Chicago
name: Ezra Cohen, MD
role: STUDY_CHAIR
affiliation: University of Pittsburgh
name: Robert Ferris, MD, PhD
role: STUDY_CHAIR
affiliation: Celgene
name: Amar Patel, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.