Safety Testing of Adding Nivolumab to Chemotherapy in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Cancer
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
3 other identifiers
interventional
40
1 country
11
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2016
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 4, 2016
CompletedFirst Posted
Study publicly available on registry
May 6, 2016
CompletedStudy Start
First participant enrolled
June 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 25, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
February 21, 2022
CompletedNovember 29, 2022
November 1, 2022
2.3 years
May 4, 2016
November 22, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Dose Limiting Toxicity (DLT)
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.
From the first dose of nivolumab to 28 days after the completion of radiation therapy.
Study Arms (4)
Arm 1 (Nivolumab + Cisplatin)
EXPERIMENTALPatients 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.
Arm 2 (Nivolumab + High-dose Cisplatin)
EXPERIMENTALPatients 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.
Arm 3 (Nivolumab + Cetuximab)
EXPERIMENTALPatients 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.
Arm 4 (Nivolumab + IMRT)
EXPERIMENTALPatients 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.
Interventions
Anti-PD-1 targeted immunotherapy
Anti-cancer alkylating agent
Epidermal Growth Factor Receptor (EGFR) antagonist
High-precision radiotherapy
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- RTOG Foundation, Inc.lead
- Bristol-Myers Squibbcollaborator
Study Sites (11)
Stanford Cancer Institute
Palo Alto, California, 94304, United States
University of Florida Cancer Center at Orlando Health
Orlando, Florida, 32806, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Louisville
Louisville, Kentucky, 40202, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Ohio State University
Columbus, Ohio, 43210, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
UPMC - Shadyside Hospital
Pittsburgh, Pennsylvania, 15232, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Inova Fairfax Hospital
Falls Church, Virginia, 22042, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Related Publications (1)
Gillison ML, Ferris RL, Harris J, Colevas AD, Mell LK, Kong C, Jordan RC, Moore KL, Truong MT, Kirsch C, Chakravarti A, Blakaj DM, Clump DA, Ohr JP, Deeken JF, Gensheimer MF, Saba NF, Dorth JA, Rosenthal DI, Leidner RS, Kimple RJ, Machtay M, Curran WJ Jr, Torres-Saavedra P, Le QT. Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504. Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):847-860. doi: 10.1016/j.ijrobp.2022.10.008. Epub 2022 Oct 11.
PMID: 36228746DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Maura Gillison, MD, PhD
RTOG Foundation
- PRINCIPAL INVESTIGATOR
Robert Ferris, MD, PhD
RTOG Foundation
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 4, 2016
First Posted
May 6, 2016
Study Start
June 1, 2016
Primary Completion
September 25, 2018
Study Completion
February 21, 2022
Last Updated
November 29, 2022
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will not share