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

NCT ID: NCT02764593

Last Updated: 2022-11-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2022-02-21

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.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Anti-PD-1 targeted immunotherapy

Cisplatin

Intervention Type: DRUG

Anti-cancer alkylating agent

IMRT

Intervention Type: RADIATION

High-precision radiotherapy

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.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Anti-PD-1 targeted immunotherapy

Cisplatin

Intervention Type: DRUG

Anti-cancer alkylating agent

IMRT

Intervention Type: RADIATION

High-precision radiotherapy

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.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Anti-PD-1 targeted immunotherapy

Cetuximab

Intervention Type: DRUG

Epidermal Growth Factor Receptor (EGFR) antagonist

IMRT

Intervention Type: RADIATION

High-precision radiotherapy

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.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Anti-PD-1 targeted immunotherapy

IMRT

Intervention Type: RADIATION

High-precision radiotherapy

Interventions

Nivolumab

Anti-PD-1 targeted immunotherapy

Intervention Type: DRUG

Cisplatin

Anti-cancer alkylating agent

Intervention Type: DRUG

Cetuximab

Epidermal Growth Factor Receptor (EGFR) antagonist

Intervention Type: DRUG

IMRT

High-precision radiotherapy

Intervention Type: RADIATION

Other Intervention Names

Opdivo; Platinol; Erbitux; Intensity Modulated Radiation Therapy

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

RTOG Foundation, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maura Gillison, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

RTOG Foundation

Robert Ferris, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

RTOG Foundation

Locations

Stanford Cancer Institute

Palo Alto, California, United States

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States

University of Louisville

Louisville, Kentucky, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

University of Florida Cancer Center at Orlando Health

Orlando, Florida, United States

Providence Portland Medical Center

Portland, Oregon, United States

UPMC - Shadyside Hospital

Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center

Houston, Texas, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36228746 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

RF 3504

Identifier Type: OTHER

Identifier Source: secondary_id

CA209-410

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG 3504

Identifier Type: -

Identifier Source: org_study_id