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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by VentiRx Pharmaceuticals Inc.
Sponsor:
Information provided by (Responsible Party):
VentiRx Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01836029
First received: April 12, 2013
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by VentiRx Pharmaceuticals Inc.:

Primary Outcome Measures:
  • To compare the efficacy of VTX-2337 plus SOC to SOC alone in prolonging the PFS of patients with recurrent or metastatic SCCHN. [ Time Frame: approximately 9 months after the last patient is randomized ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the safety of VTX-2337 plus SOC versus SOC alone by adverse events, including clinically significant changes in physical examination, peripheral blood hematology, serum chemistry, urinalysis, and ECG. [ Time Frame: Approximately 9 months after the last patient is randomized ] [ Designated as safety issue: Yes ]
  • To compare the efficacy of VTX-2337 plus SOC versus SOC alone in prolonging the OS of patients with recurrent or metastatic SCCHN. [ Time Frame: Approximately 12 months after the last patient is randomized ] [ Designated as safety issue: No ]
  • To compare the efficacy of VTX-2337 plus SOC to SOC alone on objective response rate. [ Time Frame: Approximately 9 months after the last patient is randomized ] [ Designated as safety issue: No ]
  • To compare the efficacy of VTX-2337 plus SOC to SOC alone on duration of best response. [ Time Frame: Approximately 9 months after the last patient is randomized. ] [ Designated as safety issue: No ]
  • To compare the efficacy of VTX-2337 plus SOC to SOC alone on disease control rate. [ Time Frame: Approximately 9 months after the last patient is randomized. ] [ Designated as safety issue: No ]
  • To compare the efficacy of VTX-2337 plus SOC to SOC alone on duration of disease control. [ Time Frame: Approximately 9 months after the last patient is randomized. ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • To compare the effect of immune cell subsets within the tumor on response to treatment and/or clinical outcome. [ Time Frame: Approximately 9 months after the last patient is randomized ] [ Designated as safety issue: No ]
  • To compare the genetic polymorphisms that may impact the response of patients to a TLR8 agonist or to cetuximab between the two treatment groups. [ Time Frame: Screening ] [ Designated as safety issue: No ]
  • To compare the immune biomarker response as measured by a multiplexed panel of cytokines, chemokines, and inflammatory markers between the two treatment groups. [ Time Frame: Screening, Cycle 1 Day 8, and Cycle 3 Day 8 ] [ Designated as safety issue: No ]
  • To assess PK of VTX-2337 [ Time Frame: Cycle 1 Day 8 ] [ Designated as safety issue: No ]

Estimated Enrollment: 175
Study Start Date: July 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01836029

Contacts
Contact: Kristi Manjarrez 206-689-2259

  Show 55 Study Locations
Sponsors and Collaborators
VentiRx Pharmaceuticals Inc.
Investigators
Study Chair: Ezra Cohen, MD University of Chicago
Study Chair: Robert Ferris, MD, PhD University of Pittsburgh
  More Information

No publications provided by VentiRx Pharmaceuticals Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: VentiRx Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01836029     History of Changes
Other Study ID Numbers: VRXP-A202
Study First Received: April 12, 2013
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by VentiRx Pharmaceuticals Inc.:
SCCHN
HNSCC

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Carcinoma
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Carboplatin
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014