De-Escalation Therapy for Human Papillomavirus Negative Disease

NCT03944915 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IRB19-0162
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Papilloma Virus; Squamous Cell Carcinoma; Squamous Cell Carcinoma of the Head and Neck; HPV-Related Squamous Cell Carcinoma; HNSCC

Outcome Measures

Primary Outcomes (1)

• Deep Response Rate (DRR)

  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.

  2 years

Secondary Outcomes (4)

• Progression Free Survival Rate (PFS)

  26 months

• Overall Survival Rate (OS)

  26 months

• Locoregional Control After Completing Chemoradiation

  26 months

• Distant Control After Completing Chemoradiation

  26 months

Other Outcomes (2)

• Acute and Late Toxicity During Treatment

  1 year

• Enteral Tube Dependency

  1 year

Study Arms (2)

Standard Chemotherapy

EXPERIMENTAL

Induction Therapy

Drug: Carboplatin; Drug: Paclitaxel; Drug: Nivolumab

De-escalated Chemotherapy

EXPERIMENTAL

Radiation therapy with chemotherapy

Drug: Paclitaxel; Radiation: Radiation; Drug: Hydroxyurea Pill; Drug: 5-fluorouracil; Drug: Filgrastim Injection; Drug: Cisplatin

Interventions

Carboplatin DRUG

Carboplatin will be given through IV infusions for 30-60 minutes on day 1 of each cycle. Each cycle will last 21 days. There will be 3 cycles.

Standard Chemotherapy

Paclitaxel DRUG

During Induction Therapy Paclitaxel (100 mg) will be given through IV infusions on days 1, 8 and 15 of each 21 day cycle. There will be 3 cycles. During Radiotherapy, paclitaxel will be given after a dose of radiation by IV infusion for 60 minutes after day 1 of radiotherapy.

De-escalated Chemotherapy; Standard Chemotherapy

Nivolumab DRUG

Nivolumab will be given through IV infusions at 360 mg on day 1 every 21 days for 3 cycles.

Standard Chemotherapy

Radiation RADIATION

Patients will receive 4.5-5 cycles of radiation depending on response. Those with a positive response will receive radiation for 4.5 cycles with a total radiation dose of 66 Gy. Patients with a moderate or no response will receive 5 cycles with a total radiation dose of 70-75 Gy. 2 times a day for days 1-5 followed by a rest period for days 6-13

De-escalated Chemotherapy

Hydroxyurea Pill DRUG

One dose of hydroxyurea pill by mouth at start of 5-FU infusion during radiotherapy cycle

De-escalated Chemotherapy

5-fluorouracil DRUG

5-FU will be given by IV infusion continuously for 5 days during radiotherapy cycles

Also known as: 5-FU

De-escalated Chemotherapy

Filgrastim Injection DRUG

Filgrastim shot will be given if patient has certain side effects during radiotherapy cycle on days 6-12.

Also known as: Filgrastim shot

De-escalated Chemotherapy

Cisplatin DRUG

Radiotherapy may also be given with a different chemotherapy agent called cisplatin. This is the traditional standard of care chemotherapy regimen. In this case, the radiotherapy will be given once daily for 5 days per week. Cisplatin will be administered via IV once every 21 days for 2 or 3 cycles.

De-escalated Chemotherapy

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 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
• Leukocytes ≥ 3000/mm3
• Platelets ≥ 100,000/mm3
• Absolute neutrophil count ≥ 1,500
• Hemoglobin ≥ 9.0 gm/dL
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5x upper limit of normal

You may not qualify if:

• 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.
• Has active autoimmune disease that has required systemic therapy in the past year (i.e. with steroids or immunosuppressive drugs). Replacement therapy e.g. levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary insufficiency, etc. are not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has a history of HIV.
• Has known active Hepatitis B or hepatitis C. If eradicated, patient is eligible.
• Has received a live vaccine within 28 days of planned start of study therapy.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University Of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Rosenberg AJ, Juloori A, Jelinek MJ, Agrawal N, Cursio JF, Cipriani N, Lingen MW, Izumchenko E, Katipally R, Chin J, Ginat D, Pasternak-Wise O, Gooi Z, Blair E, Pearson AT, Haraf DJ, Vokes EE. Neoadjuvant Nivolumab Plus Chemotherapy Followed by Response-Stratified Chemoradiation Therapy in HPV-Negative Head and Neck Cancer: The DEPEND Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2025 May 1;11(5):492-501. doi: 10.1001/jamaoncol.2025.0081.

  PMID: 40048190 DERIVED

MeSH Terms

Conditions

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

Interventions

Carboplatin; Paclitaxel; Nivolumab; Radiation; Hydroxyurea; Fluorouracil; Filgrastim; Cisplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Physical Phenomena; Urea; Amides; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Dr. Ari Rosenberg
• Organization: University of Chicago

arirosenberg@bsd.uchicago.edu

855-702-8222

Study Officials

• Everett Vokes, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: May 10, 2019
• Study Start: August 26, 2019
• Primary Completion: November 1, 2023
• Study Completion: November 1, 2023
• Last Updated: May 11, 2025
• Results First Posted: May 11, 2025

Record last verified: 2025-04

Locations

US (1)