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Safety Testing of Adding Nivolumab to Chemotherapy in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Cancer

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: NCT02764593
Recruitment Status : Active, not recruiting
First Posted : May 6, 2016
Last Update Posted : June 19, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
RTOG Foundation, Inc.

Brief Summary:
This study will evaluate the safety of adding nivolumab to several chemotherapy platforms with weekly cisplatin, high-dose cisplatin, cetuximab or radiation therapy alone.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma (HNSCC) Drug: Nivolumab Drug: Cisplatin Drug: Cetuximab Radiation: IMRT Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety Evaluations of Nivolumab (Anti-PD-1) Added To Chemotherapy (CRT) Platforms In Patients With Intermediate And High-Risk Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma
Study Start Date : June 2016
Actual Primary Completion Date : September 25, 2018
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1 (Nivolumab + Cisplatin)
Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cisplatin will be given weekly. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
Drug: Nivolumab
Anti-PD-1 targeted immunotherapy
Other Name: Opdivo

Drug: Cisplatin
Anti-cancer alkylating agent
Other Name: Platinol

Radiation: IMRT
High-precision radiotherapy
Other Name: Intensity Modulated Radiation Therapy

Experimental: Arm 2 (Nivolumab + High-dose Cisplatin)
Patients will receive Nivolumab via IV administration starting 14 days prior to IMRT, then Day 1 of IMRT and then every 21 days for 6 doses. Cisplatin will be given every 21 days for 3 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
Drug: Nivolumab
Anti-PD-1 targeted immunotherapy
Other Name: Opdivo

Drug: Cisplatin
Anti-cancer alkylating agent
Other Name: Platinol

Radiation: IMRT
High-precision radiotherapy
Other Name: Intensity Modulated Radiation Therapy

Experimental: Arm 3 (Nivolumab + Cetuximab)
Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cetuximab will be given for 7 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
Drug: Nivolumab
Anti-PD-1 targeted immunotherapy
Other Name: Opdivo

Drug: Cetuximab
Epidermal Growth Factor Receptor (EGFR) antagonist
Other Name: Erbitux

Radiation: IMRT
High-precision radiotherapy
Other Name: Intensity Modulated Radiation Therapy

Experimental: Arm 4 (Nivolumab + IMRT)
Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
Drug: Nivolumab
Anti-PD-1 targeted immunotherapy
Other Name: Opdivo

Radiation: IMRT
High-precision radiotherapy
Other Name: Intensity Modulated Radiation Therapy




Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) [ Time Frame: From the first dose of nivolumab to 28 days after the completion of radiation therapy. ]

    A nivolumab attributable, dose-limiting toxicity (DLT) will be defined as follows:

    1) Any ≥ grade 3 adverse event (CTCAE, v. 4) that is related to nivolumab that does not resolve to grade 1 or less within 28 days; 2) A delay in radiotherapy of > 2 weeks due to toxicity related to nivolumab; 3) Inability to complete radiotherapy due to toxicity related to nivolumab; 4) Inability to receive an adequate dose (≥ 70%) of cisplatin (Arm 1 and 2) or cetuximab (Arm 3) due to toxicity definitely related to nivolumab.




Information from the National Library of Medicine

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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:

  • Histologically or cytologically-confirmed diagnosis of HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx.
  • Intermediate-risk group: Oropharynx cancer that is p16-positive by immunohistochemistry with smoking status > 10 Pack-years, stage T1-2N2b-N3 OR ≤ 10 pack-years, stage T4N0-N3 or T1-3N3.
  • High-risk group: Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer, stage T1-2N2a-N3 or T3-4-N0-3 based on the following diagnostic workup:

    • Mandatory submission of H&E and p16 stained slides for central review of p16 staining is required for oropharyngeal patients and H&E stained slide block (or punch biopsy of paraffin block) for PD-L1 expression analysis for all patients
    • History/physical examination within 28 days prior to registration
    • Examination by Radiation Oncologist, Medical Oncologist, and Ear, Nose, Throat (ENT) or Head & Neck Surgeon within 28 days prior to registration
    • Fiberoptic exam with laryngopharyngoscopy within 28 days prior to registration
    • Diagnostic quality, cross sectional imaging of the thorax within 28 days prior to registration; 18-F-FDG-PET/CT or conventional CT are acceptable.
    • Diagnostic quality CT or MRI of neck, with contrast, within 28 days prior to registration; a 18-F-FDG-PET/CT of the neck only is acceptable as a substitute if the CT is of diagnostic quality and with IV contrast.
  • Age ≥ 18 years
  • The trial is open to both genders

Exclusion Criteria:

  • Definitive clinical or radiologic evidence of distant (beyond cervical lymph node and neck tissue) metastatic disease.
  • Patients with oral cavity cancer are excluded from participation if resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist.
  • Carcinoma of the neck of unknown primary site origin (even if p16-positive).
  • Absence of RECIST, v. 1.1 defined measurable disease.
  • Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. Patients with RECIST, v. 1.1 evaluable remaining cancer either in the neck or primary site remain eligible.
  • Simultaneous primary cancers or separate bilateral primary tumor sites.
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
  • Prior systemic chemotherapy for the study cancer.
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
  • Patients with active autoimmune disease, with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis.
  • Use of systemic corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled or topical steroids.
  • Known immunosuppressive disease, for example HIV infection or history of bone marrow transplant or chronic lymphocytic leukemia (CLL).

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): NCT02764593


Locations
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United States, California
Stanford Cancer Institute
Palo Alto, California, United States, 94304
United States, Florida
University of Florida Cancer Center at Orlando Health
Orlando, Florida, United States, 32806
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Ohio
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106
Ohio State University
Columbus, Ohio, United States, 43210
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
UPMC - Shadyside Hospital
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
RTOG Foundation, Inc.
Bristol-Myers Squibb
Investigators
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Principal Investigator: Maura Gillison, MD, PhD RTOG Foundation
Principal Investigator: Robert Ferris, MD, PhD RTOG Foundation
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Responsible Party: RTOG Foundation, Inc.
ClinicalTrials.gov Identifier: NCT02764593    
Other Study ID Numbers: RTOG 3504
RF 3504 ( Other Identifier: RTOG Foundation )
CA209-410 ( Other Identifier: Bristol-Myers Squibb )
First Posted: May 6, 2016    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by RTOG Foundation, Inc.:
Head and Neck Squamous Cell Carcinoma
HNSCC
Nivolumab
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
Nivolumab
Cetuximab
Antineoplastic Agents
Antineoplastic Agents, Immunological