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

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: NCT03254927
Recruitment Status : Active, not recruiting
First Posted : August 21, 2017
Last Update Posted : November 4, 2020
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics

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.

Condition or disease Intervention/treatment Phase
Advanced Head and Neck Squamous Cell Carcinoma Drug: CDX-3379 and cetuximab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 27, 2018
Actual Primary Completion Date : September 16, 2020
Estimated Study Completion Date : August 2021


Arm Intervention/treatment
Experimental: CDX-3379 and cetuximab
During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.
Drug: CDX-3379 and cetuximab
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 Measures :
  1. Objective Response Rate [ 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. ]
    The percentage of patients who achieve a complete response or partial response per RECIST 1.1 criteria.


Secondary Outcome Measures :
  1. Clinical Benefit Response (CBR) [ Time Frame: Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years ]
    The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months

  2. Duration of response (DOR) [ Time Frame: First occurrence of a documented objective response to disease progression or death (up to approximately 2 years) ]
    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

  3. Progression-free Survival (PFS) [ Time Frame: From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years) ]
    The time from start of study drug to time of progression or death, whichever occurs first

  4. Overall Survival (OS) [ Time Frame: The time from start of study drug to death from any cause (up to approximately 2 years) ]
    The time from start of study drug to death

  5. Incidence of drug related adverse events, serious drug related adverse events, dose-limiting toxicities and laboratory test abnormalities [Safety and Tolerability] [ Time Frame: Following at least one dose of study treatment through 30 days after last dose of CDX-3379. ]
    Safety and tolerability of CDX-3379 in combination with cetuximab as determined by vital sign measurements, clinical laboratory tests, physical exams, ECGs and the incidence and severity of adverse events.

  6. Pharmacokinetic evalution [ Time Frame: From start of study drug through 30 day follow up ]
    CDX-3379 serum concentration will be measured

  7. Immunogenicity evaulation [ Time Frame: Prior to each dose of study treatment through 30 day follow up ]
    Serum samples will be obtained for assessment of human anti-CDX-3379 antibodies

  8. Tumor DNA biomarkers. [ Time Frame: Tumor tissue is obtained during screening window via single biopsy procedure. ]
    Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy.



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:

  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.

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): NCT03254927


Locations
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United States, Arizona
The University of Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06511
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush University Medical center
Chicago, Illinois, United States, 60612
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
United States, Pennsylvania
University of Pennsylvania Hospital, Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Celldex Therapeutics
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT03254927    
Other Study ID Numbers: CDX3379-04
First Posted: August 21, 2017    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celldex Therapeutics:
Erbitux
Cetuximab
Oral Cancer
Oropharyngeal cancer
Laryngeal cancer
Head and Neck Squamous Cell Carcinoma
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
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents