Neoadjuvant Immunoradiotherapy in Head & Neck Cancer (NIRT 2-HNC)

NCT04938609 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 2020000720 NIRT 2
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the efficacy of neoadjuvant immunoradiotherapy (NIRT) prior to surgery for the treatment of stage III and IVA HPV- HNSCC.

Conditions

Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

HNSCC; radiation; surgery; pembrolizumab; Phase 2; immunotherapy; antibodies

Outcome Measures

Primary Outcomes (1)

• To determine the pathologic response rate (MPR + pCR) at time of surgery

  Prior to surgery neoadjuvant immunoradiotherapy (NIRT) with stereotactic body radiation therapy (SBRT) + pembrolizumab in stage III-IVA HPV-negative HNSCC patients.

  52 weeks

Secondary Outcomes (10)

• Overall Response Rate

  5 years

• Clinical swallowing evaluation assessed by VFSS

  5 years

• Quality of Life assessed by PSS-HN

  5 years

• Quality of Life assessed by FACT-H&N

  5 years

• Quality of Life assessed by MDASI-HN

  5 years

Study Arms (1)

Pembrolizumab + SBRT + Surgery

EXPERIMENTAL

Pembrolizumab administration (3 dose) every 3 weeks and 1 dose before radiation (5 days) therapy followed by an additional administration of Pembrolizumab (2 doses) prior to restaging and surgical resection followed by risk-adapted adjuvant therapy, per standard of care. Patient will then be treated with adjuvant pembrolizumab every 3 weeks for 14 additional doses (17 doses total)

Drug: Pembrolizumab; Radiation: Stereotactic Body Radiation Therapy (5 days); Procedure: Surgical Resection

Interventions

Pembrolizumab DRUG

Pembrolizumab is a humanized anti-PD-1 mAb of the IgG4/kappa isotype with a stabilizing S228P sequence alteration in the Fc region.

Also known as: Keytruda

Pembrolizumab + SBRT + Surgery

Stereotactic Body Radiation Therapy (5 days) RADIATION

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

Pembrolizumab + SBRT + Surgery

Surgical Resection PROCEDURE

Surgical Resection of Tumor

Pembrolizumab + SBRT + Surgery

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent.
• Histologically confirmed diagnosis of stage III-IVA HPV-negative HNSCC who are planned for surgical resection and in the opinion of the investigator are able to safely undergo neoadjuvant anti-PD-1 and radiation will be enrolled in this study. Oral cavity, hypopharynx, and larynx cancer are not required to undergo HPV testing by p16 IHC as by convention these tumor locations are assumed to be HPV-negative
• Male participants:
• A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 75 days, corresponding to time needed to eliminate any study treatment) plus an additional 120 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant (see Appendix 3),or breastfeeding and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 75 days (corresponding to time needed to eliminate any study treatment) plus 30 days (a menstruation cycle) after the last dose of study treatment.
• The participant must provide (or legally acceptable representative if applicable) written informed consent for the trial.
• Have provided archival tumor tissue sample collected within the last 6 months or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Note: If submitting unstained slides, slides should be submitted to the testing laboratory within 14 days from the date slides are cut. For archival tissue samples collected \>6 months from screening, PI approval is required.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 10 days prior to the date of enrollment
• Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.

You may not qualify if:

• A WOCBP who has a positive serum or urine pregnancy test within 72 hours prior to first dose of pembrolizumab (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to enrollment
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy to the head and neck region.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) or other solid tumor or hematologic malignancy that have undergone potentially curative therapy outside of the head and neck are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Sponsors & Collaborators

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

Study Sites (3)

University of San Diego

San Diego, California, 92037, United States

Location

Portland Providence Medical Center

Portland, Oregon, 97213, United States

Location

Providence St. Vincent Medical Center

Portland, Oregon, 97225, United States

Location

MeSH Terms

Conditions

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

Interventions

pembrolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• R. Bryan Bell, MD, DDS, FACS

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 24, 2021
• Study Start: January 11, 2022
• Primary Completion (Estimated): January 11, 2027
• Study Completion (Estimated): January 11, 2031
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (3)