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A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma

Primary Purpose

Advanced Head and Neck Squamous Cell Carcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CDX-3379 and cetuximab
Sponsored by
Celldex Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Head and Neck Squamous Cell Carcinoma focused on measuring Erbitux, Cetuximab, Oral Cancer, Oropharyngeal cancer, Laryngeal cancer, Head and Neck Squamous Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologically or cytologically confirmed head and neck squamous cell carcinoma.
  2. Human papilloma virus (HPV) negative tumor.
  3. Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate.
  4. Prior treatment with cetuximab with tumor progression during or within 6 months after completing treatment.
  5. Measurable disease.
  6. Life expectancy ≥ 12 weeks.
  7. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 6 months following last treatment.
  8. Willingness to undergo a tumor biopsy prior to starting treatment (or if biopsy is not feasible, provide archival tissue).

Exclusion Criteria:

  1. Previous treatment with CDX-3379 or other anti-ErbB3 targeted agents.
  2. Nasal, paranasal sinus, or nasopharyngeal carcinoma, aside from WHO Type I and II (keratinizing, non-EBV positive) nasopharyngeal carcinoma which will be allowed.
  3. Major surgery within 4 weeks prior to first dose of study treatment.
  4. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment.
  5. Monoclonal based therapies within 4 weeks (excluding cetuximab) and all other immunotherapy within 2 weeks prior to first dose of study treatment.
  6. Other prior malignancy, active within 3 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast.
  7. Active, untreated central nervous system metastases.
  8. Active autoimmune disease or documented history of autoimmune disease.
  9. Significant cardiovascular disease including CHF or poorly controlled hypertension.

Sites / Locations

  • The University of Arizona Cancer Center
  • Yale Cancer Center
  • Emory University Winship Cancer Institute
  • Rush University Medical center
  • Washington University School of Medicine
  • University of Cincinnati
  • University of Pennsylvania Hospital, Abramson Cancer Center
  • UPMC Hillman Cancer Center
  • Medical University of South Carolina
  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CDX-3379 and cetuximab

Arm Description

During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.

Outcomes

Primary Outcome Measures

Objective Response Rate
The percentage of patients who achieve a complete response or partial response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.

Secondary Outcome Measures

Clinical Benefit Response (CBR)
The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks
Duration of Response (DOR)
The interval from which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) until the first date that progressive disease is objectively documented
Progression-free Survival (PFS)
The time from start of study drug to time of progression or death, whichever occurs first
Overall Survival (OS)
The time from start of study drug to death
Incidence of Adverse Events [Safety and Tolerability]
Safety and tolerability of CDX-3379 in combination with cetuximab as determined by incidence and severity of adverse events. Percentage of patients reporting one or more adverse events.
Tumor DNA Biomarkers.
Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy. Objective response rate for subset of patients with FAT1 positive tumor is reported.

Full Information

First Posted
August 17, 2017
Last Updated
March 7, 2023
Sponsor
Celldex Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT03254927
Brief Title
A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma
Official Title
A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of CDX-3379 in Combination With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision based on emerging risk-benefit profile
Study Start Date
March 27, 2018 (Actual)
Primary Completion Date
September 16, 2020 (Actual)
Study Completion Date
December 16, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celldex Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a study to determine the clinical benefit (how well the drug works), safety and tolerability of combining CDX-3379 and cetuximab. The study will enroll patients with advanced head and neck squamous cell carcinoma who have previously received cetuximab and progressed.
Detailed Description
CDX-3379 is a fully human monoclonal antibody that binds to a molecule called human epidermal growth factor receptor 3 (HER3 or ErbB3) found on certain cells and may act to promote anti-tumor effects. Cetuximab is a human monoclonal antibody that blocks EGFR, a protein receptor that regulates cell growth. This study will evaluate the safety, tolerability and efficacy of CDX-3379 in combination with cetuximab in patients with advanced head and neck squamous cell carcinoma who have previously received cetuximab and progressed. Eligible patients that enroll in the study will be given the dose of 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab. Up to 45 patients will be enrolled. All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Head and Neck Squamous Cell Carcinoma
Keywords
Erbitux, Cetuximab, Oral Cancer, Oropharyngeal cancer, Laryngeal cancer, Head and Neck Squamous Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CDX-3379 and cetuximab
Arm Type
Experimental
Arm Description
During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.
Intervention Type
Drug
Intervention Name(s)
CDX-3379 and cetuximab
Intervention Description
Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
The percentage of patients who achieve a complete response or partial response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.
Time Frame
The proportion of evaluable patients who achieve a best overall response of complete or partial response according to RECIST 1.1 assessed up to 24 months.
Secondary Outcome Measure Information:
Title
Clinical Benefit Response (CBR)
Description
The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks
Time Frame
Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years
Title
Duration of Response (DOR)
Description
The interval from which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) until the first date that progressive disease is objectively documented
Time Frame
First occurrence of a documented objective response to disease progression or death (up to approximately 2 years)
Title
Progression-free Survival (PFS)
Description
The time from start of study drug to time of progression or death, whichever occurs first
Time Frame
From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years)
Title
Overall Survival (OS)
Description
The time from start of study drug to death
Time Frame
The time from start of study drug to death from any cause (up to approximately 2 years)
Title
Incidence of Adverse Events [Safety and Tolerability]
Description
Safety and tolerability of CDX-3379 in combination with cetuximab as determined by incidence and severity of adverse events. Percentage of patients reporting one or more adverse events.
Time Frame
Following at least one dose of study treatment through 30 days after last dose of CDX-3379.
Title
Tumor DNA Biomarkers.
Description
Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy. Objective response rate for subset of patients with FAT1 positive tumor is reported.
Time Frame
Tumor tissue is obtained during screening window via single biopsy procedure.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed head and neck squamous cell carcinoma. Human papilloma virus (HPV) negative tumor. Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate. Prior treatment with cetuximab with tumor progression during or within 6 months after completing treatment. Measurable disease. Life expectancy ≥ 12 weeks. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 6 months following last treatment. Willingness to undergo a tumor biopsy prior to starting treatment (or if biopsy is not feasible, provide archival tissue). Exclusion Criteria: Previous treatment with CDX-3379 or other anti-ErbB3 targeted agents. Nasal, paranasal sinus, or nasopharyngeal carcinoma, aside from WHO Type I and II (keratinizing, non-EBV positive) nasopharyngeal carcinoma which will be allowed. Major surgery within 4 weeks prior to first dose of study treatment. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment. Monoclonal based therapies within 4 weeks (excluding cetuximab) and all other immunotherapy within 2 weeks prior to first dose of study treatment. Other prior malignancy, active within 3 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast. Active, untreated central nervous system metastases. Active autoimmune disease or documented history of autoimmune disease. Significant cardiovascular disease including CHF or poorly controlled hypertension.
Facility Information:
Facility Name
The University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Emory University Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush University Medical center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
University of Pennsylvania Hospital, Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
UPMC Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31308059
Citation
Duvvuri U, George J, Kim S, Alvarado D, Neumeister VM, Chenna A, Gedrich R, Hawthorne T, LaVallee T, Grandis JR, Bauman JE. Molecular and Clinical Activity of CDX-3379, an Anti-ErbB3 Monoclonal Antibody, in Head and Neck Squamous Cell Carcinoma Patients. Clin Cancer Res. 2019 Oct 1;25(19):5752-5758. doi: 10.1158/1078-0432.CCR-18-3453. Epub 2019 Jul 15.
Results Reference
derived

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A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma

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