A Randomized, Double-Blind Phase II Study of Adjuvant Pembrolizumab Versus Placebo in Head and Neck Cancers at High Risk for Recurrence- the PATHWay Study

NCT02841748 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB15-1632
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

A placebo-controlled, randomized study using adjuvant pembrolizumab treatment for one year in order to potentially improve progression free survival in a squamous cell carcinoma of the head and neck cohort at high-risk for recurrence.

Conditions

Head and Neck Cancer; Squamous Cell Carcinoma of the Head and Neck

Keywords

Pembrolizumab; HNSCC

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Measured using RECIST 1.1

  2 years

Secondary Outcomes (3)

• Progression free survival in gene expression profile (GEP) positive patients

  2 years

• Progression free survival in gene expression profile in PD-L1 >10% positive patients

  2 years

• Overall survival in the overall patient population, and in gene expression signature (GES) positive or PD-L1 positive (≥10%) patients

  2 years

Study Arms (2)

Pembrolizumab

EXPERIMENTAL

200mg, every three weeks, iv, x 1 year

Drug: Pembrolizumab

Placebo

EXPERIMENTAL

iv, every 3 weeks, x 1 year

Drug: Placebo

Interventions

Pembrolizumab DRUG

200mg, every three weeks, iv, x 1 year

Pembrolizumab

Placebo DRUG

iv, every three weeks, x 1 year

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed head and neck cancer (Squamous cell histology as well as HPV+ and/or EBV+ head and neck tumors), Stages IVA, IVB, and select cases of Stage III.
• HPV status required prior to randomization for oropharyngeal primary tumors
• EBV status is required prior to randomization for nasopharyngeal primary tumors
• Completed curative intent therapy, without additional standard of care curative intent therapy feasible within 20 weeks prior to study enrollment
• After prior curative intent treatment for HNC have estimated risk of recurrence ≥ 40-50% and fall into one of the below categories (A, OR B, OR C, OR D, OR E). While exact estimation of the risk of recurrence can be difficult the following categories will be included reflecting patients at substantial risk for tumor recurrence or already with early evidence of recurrence:
• A: Any of the below HNC patients are eligible for adjuvant treatment on this protocol AFTER completion of curative intent therapy:
• HPV(-) HNC: N2C, N3, bulky N2B disease (≥ 5cm LN/tumor conglomerate).
• HPV(+) HNC: N2C, N3, AND ≥ 10 pack years of tobacco use
• HPV(+) HNC with multilevel nodal involvement, AND bulky N2B disease (≥ 5cm LN/tumor conglomerate), AND ≥ 10 pack years of tobacco use
• EBV(+) NPC may be eligible if other criteria under A, or alternative criteria B, or C, or D, or E are met.
• HNC with supraclavicular or mediastinal nodal involvement (any HPV or EPV status ) at time of curative intent treatment and were treated as part of curative intent therapy
• Residual mass in area of prior tumor that on biopsy does not show residual tumor, is equivocal/not highly-suspicious on imaging but remains of concern, requires close follow-up AND is not resected/amenable to resection OR immediate palliative treatment.
• Non-responders to induction chemotherapy (PD on induction, or lack of tumor shrinkage (\< 15% per RECIST)
• Interrupted treatment course or lower than intended radiation dose - i.e. interruption of radiation by ≥ 3 weeks (cumulative), or delivery of ≤ 50 Gy as part of a radiation based treatment (that was NOT a de-escalation approach).
• B: Patient treated with salvage treatment (i.e. salvage surgery or re-irradiation) for residual or recurrent tumor after prior radiation based therapy (either HPV+ or HPV- or EBV+) AND not a candidate for additional curative intent therapy (for various reasons including poor performance status, comorbidities, refusal of patient, prior radiation or re-irradiation, etc). Positive margins or residual tumor may still be acceptable (see D)). Patients should also not be appropriate for systemic palliative therapy (e.g. in the case of overt disease).

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Has hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy or typical side effects from radiotherapy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence live expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy).
• Has known active (=growing) central nervous system (CNS) metastases and/or carcinomatous meningitis. Radiation or resected brain metastasis are acceptable if clinically stable.
• 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 known history of, or any evidence of active, non-infectious pneumonitis.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (4)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

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

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Alexander Pearson, M.D.

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: July 22, 2016
• Study Start: May 10, 2017
• Primary Completion (Estimated): June 20, 2026
• Study Completion (Estimated): June 25, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-09

Locations

US (4)