Neoadjuvant Immunoradiotherapy in Head & Neck Cancer

NCT03247712 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: NIRT-HNC
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety of neoadjuvant immunoradiotherapy as a safe means of down-staging Head and Neck Squamous Cell Carcinoma (HNSCC) prior to surgical resection.

Conditions

Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

HNSCC; radiation; surgery; phase 1; immunotherapy; nivolumab; antibodies

Outcome Measures

Primary Outcomes (1)

• Number of patients with an Unplanned Delay to Surgery [Safety and Tolerability of Neoadjuvant Treatment]

  Safety endpoint: Number of patients with an Unplanned Delay to Surgery defined as any change to scheduled surgery date considered to be at least possibly related to neoadjuvant treatment.

  6 weeks

Secondary Outcomes (1)

• Number of patients with decrease in tumor size or number of lymph nodes involved [Efficacy of Neoadjuvant Treatment]

  6 weeks

Study Arms (4)

Treatment Cohort 1

EXPERIMENTAL

Nivolumab administration (3 doses) and radiation (5 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).

Drug: Nivolumab; Procedure: Surgical Resection; Radiation: Radiation (5 days)

Treatment Cohort 2

EXPERIMENTAL

Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).

Drug: Nivolumab; Procedure: Surgical Resection; Radiation: Radiation (3 days)

Treatment Cohort 3

EXPERIMENTAL

Radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).

Drug: Nivolumab; Procedure: Surgical Resection; Radiation: Radiation (3 days)

Treatment Cohort 4

EXPERIMENTAL

Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).

Drug: Nivolumab; Procedure: Surgical Resection; Radiation: Radiation (3 days)

Interventions

Nivolumab DRUG

Nivolumab 240mg IV q2wks or 480mg IV q4wks

Also known as: Opdivo

Treatment Cohort 1; Treatment Cohort 2; Treatment Cohort 3; Treatment Cohort 4

Surgical Resection PROCEDURE

Surgical Resection of Tumor

Treatment Cohort 1; Treatment Cohort 2; Treatment Cohort 3; Treatment Cohort 4

Radiation (5 days) RADIATION

8Gy x 5 (Mon-Fri) GTV+3mm

Treatment Cohort 1

Radiation (3 days) RADIATION

8Gy x 3 (Monday, Wednesday, Friday) GTV+3mm

Treatment Cohort 2; Treatment Cohort 3; Treatment Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with squamous cell carcinoma of the head and neck region, (including mucosal,cutaneous, or nodal) who are planned for surgical resection and in the opinion of the investigator are able to safely undergo neoadjuvant anti-PD-1 and radiation. In addition, the following are eligible (but will not contribute toward total accrual): non-surgical cases that are planned for palliative RT or that refuse or are unfit for definitive concurrent chemotherapy.
• HPV status as determined by p16 immunostain
• Cohort 3: HPV-positive patients only
• Cohort 4: HPV-negative patients only
• Age 18 years or above with ability to give informed consent, comply with the protocol, and sign a study-specific consent document. Patients with history of psychiatric illness must be judged by the investigator as able to understand the investigational nature and risks associated with the therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status deemed suitable by investigator for study requirements.
• Laboratory values (most recent), must be within 6 weeks of week 0 on study:
• WBC ≥ 2000/uL, ANC ≥ 1000/uL
• Hgb \> 8g/dL (patients may be transfused to reach this level)
• Platelets \> 50,000 cells/mm3
• Creatinine ≤ 3 x ULN
• AST/ALT ≤ 5 x ULN for subjects without liver metastasis; or ≤ 8 x ULN for subjects with liver metastasis, \[per investigator brochure\]
• Total bilirubin ≤ 3 x ULN, (except subjects with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• Negative pregnancy test (bHCG urine or serum, women of childbearing potential only)
• Women of child-bearing potential (WOCBP) must agree to follow adequate contraceptive practices to avoid pregnancy for the duration of treatment with nivolumab plus 5 half-lives of nivolumab (75 days) plus 30 days (duration of ovulatory cycle) for a total of 105 days post-treatment completion.

You may not qualify if:

• Any clinical factors such as bleeding, active infection, or psychiatric factors that in the judgment of the investigator would preclude safe participation and compliance with study procedures.
• HNSCC for which radiation is not indicated during normal treatment course.
• Need for chronic maintenance with oral steroids ≥20mg daily prednisone equivalent; inhaled, topical or non-absorbed steroids are acceptable.

Sponsors & Collaborators

• Providence Health & Services: lead
• Providence Cancer Center, Earle A. Chiles Research Institute: collaborator

Study Sites (1)

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Related Publications (1)

• Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, Patel AA, Cheng AC, Watters AL, Bifulco C, Morris G, Rushforth L, Nemeth S, Urba WJ, Gough M, Bell RB. Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma. J Immunother Cancer. 2021 May;9(5):e002485. doi: 10.1136/jitc-2021-002485.

  PMID: 33963014 DERIVED

Related Links

• Providence Cancer Center

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Nivolumab; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Physical Phenomena

Study Officials

• Rom Leidner, MD

  Providence Health and Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: August 14, 2017
• Study Start: January 15, 2018
• Primary Completion: February 13, 2020
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)