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.

University of Chicago4 sites in 1 country100 target enrollmentMay 10, 2017

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

InterventionsPembrolizumab Placebo

DrugsPembrolizumab Placebo

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: Head and Neck Cancer
Sponsor: University of Chicago
Enrollment: 100
Locations: 4
Primary Endpoint: Progression free survival
Status: Active, not recruiting
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

May 10, 2017

End Date

June 25, 2026

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University of Chicago

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•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.

Arms & Interventions

Pembrolizumab

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

Intervention: Pembrolizumab

Placebo

iv, every 3 weeks, x 1 year

Intervention: Placebo

Outcomes

Primary Outcomes

Progression free survival

Time Frame: 2 years

Measured using RECIST 1.1

Secondary Outcomes

Progression free survival in gene expression profile in PD-L1 >10% positive patients(2 years)
Progression free survival in gene expression profile (GEP) 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)