Clinical Trials/NCT03944915

NCT03944915

Completed

Phase 2

A Phase II Trial of Carboplatin, Paclitaxel, and Nivolumab Induction Therapy Followed by Response-stratified Locoregional Therapy for Patients With Locally Advanced, HPV-negative Head and Neck Cancer. The DEPEND Trial.

University of Chicago1 site in 1 country35 target enrollmentAugust 26, 2019

Overview

Phase: Phase 2
Intervention: Hydroxyurea Pill
Conditions: Human Papilloma Virus
Sponsor: University of Chicago
Enrollment: 35
Locations: 1
Primary Endpoint: Deep Response Rate (DRR)
Status: Completed
Last Updated: 11 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is looking to see if nivolumab, an immunotherapy drug, given with carboplatin and paclitaxel (2 chemotherapy agents) during induction therapy in advanced stage HPV negative patients can significantly shrink the subject's cancer.

Registry

clinicaltrials.gov

Start Date

August 26, 2019

End Date

November 1, 2023

Last Updated

11 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Chicago

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must have pathologically confirmed locally advanced, non-metastatic, HPV-negative head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, nasopharynx, larynx, or sinuses.
•Stage IV disease with the exception of nasopharyngeal tumor-3, node-2 (stage III) based of American Joint Committee on Cancer staging 8th edition
•If a primary oropharyngeal squamous cell carcinoma is diagnosed, HPV must be ruled out by immunohistochemistry.
•Availability of ≥10 unstained 5 micron slides. Patients who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study.
•Patients must be at least 18 years of age.
•Measurable disease (either primary site and/or nodal disease) by RECIST criteria.
•No previous radiation or chemotherapy for a head and neck cancer.
•No complete surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy/excision of the tumor with residual measurable disease is acceptable.) No surgical procedures or biopsies will occur after baseline scans are performed and measurable lesions are identified.
•Eastern Cooperative Oncology Group performance status 0-1
•Normal Organ Function

Exclusion Criteria

•Unequivocal demonstration of distant metastatic disease (M1 disease).
•Unidentifiable primary site.
•Inter-current medical illnesses which would impair patient tolerance to therapy or limit survival. This includes but is not limited to ongoing or active infection, immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance. Patients with clinically stable and/or chronically managed medical illnesses that are not symptomatic and/or are not expected to impact treatment on protocol are still eligible (conditions to be reviewed by the PI to confirm eligibility)
•Prior surgical therapy other than incisional/excisional biopsy or organ-sparing procedures such as debulking of airway-compromising tumors. Residual measurable tumor is required for enrollment as discussed above.
•Patients receiving other investigational agents.
•Diagnosis of immunodeficiency or is receiving systemic steroid therapy in excess of physiologic dose or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
•Known history of active tuberculosis (Bacillus Tuberculosis infection).
•Hypersensitivity to nivolumab or any other drug used in this protocol.
•Prior systemic anti-cancer treatment within the last 8 weeks.
•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 life expectancy in the subsequent 3 years without active treatment.

Arms & Interventions

De-escalated Chemotherapy

Radiation therapy with chemotherapy

Intervention: Hydroxyurea Pill

Standard Chemotherapy

Induction Therapy

Intervention: Carboplatin

Standard Chemotherapy

Induction Therapy

Intervention: Paclitaxel

Standard Chemotherapy

Induction Therapy

Intervention: Nivolumab

De-escalated Chemotherapy

Radiation therapy with chemotherapy

Intervention: Paclitaxel

De-escalated Chemotherapy

Radiation therapy with chemotherapy

Intervention: Radiation

De-escalated Chemotherapy

Radiation therapy with chemotherapy

Intervention: 5-fluorouracil

De-escalated Chemotherapy

Radiation therapy with chemotherapy

Intervention: Filgrastim Injection

De-escalated Chemotherapy

Radiation therapy with chemotherapy

Intervention: Cisplatin

Outcomes

Primary Outcomes

Deep Response Rate (DRR)

Time Frame: 2 years

DRR is 50% or greater response to induction therapy based on RECIST criteria. The objective is to intensify induction chemotherapy with the addition of an immune checkpoint inhibitor aimed at increasing the proportion of patients achieving a deep tumor response in order to subsequently allow risk-adapted definitive chemoradiotherapy in advanced stage HPV negative head and neck squamous cell cancer patients.