Personalized, Adaptive Treatment for Locally Advanced Head and Neck Cancer

NCT06005324 | Recruiting Phase 1 FDA Drug FDA Device

• 1 other identifier: IRB23-0095
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial will assess whether or not blood based biomarker testing can be used to personalize cancer treatment for patients with locally advanced head and neck cancer.

Conditions

HPV-Negative Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Percentage of participants that complete study treatment and provide all required research blood draws.

  To be measured at end of treatment period (9 weeks)

• Determine if ctDNA levels is predicative of disease response

  Researchers will look at amount of ctDNA in the blood to determine if it correlates to disease response based on imaging results per RECIST v1.1.

  To be measured at end of treatment period (9 weeks)

Secondary Outcomes (2)

• Number of participants with side effects related to study treatment

  To be measured at 3 months after end of treatment period

• Long Term Disease Response based on RECIST 1.1

  To be assessed at 2 years after end of treatment period

Study Arms (3)

Induction Treatment Arm

OTHER

All participants will receive 3 cycles (9 weeks) of chemotherapy with paclitaxel, carboplatin, and cetuximab.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Cetuximab

De-Escalation CRT Cohort

EXPERIMENTAL

After completing induction chemotherapy, participants that have significant disease response by imaging will receive low dose radiation treatment with additional chemotherapy (CRT). Investigator will choose the appropriate chemotherapy backbone to be given during CRT.

Radiation: Low Dose Radiation; Drug: Cisplatin; Drug: TFHX Regimen

Standard Treatment Cohort

ACTIVE COMPARATOR

After completing induction chemotherapy, participants that have limited disease response by imaging will receive standard dose radiation treatment with additional chemotherapy (CRT). Investigator will choose the appropriate chemotherapy backbone to be given during CRT.

Radiation: Standard Dose Radiation; Drug: Cisplatin; Drug: TFHX Regimen

Interventions

Paclitaxel DRUG

Given as part of induction chemotherapy.

Induction Treatment Arm

Carboplatin DRUG

Given as part of induction chemotherapy.

Induction Treatment Arm

Cetuximab DRUG

Given as part of induction chemotherapy.

Induction Treatment Arm

Standard Dose Radiation RADIATION

Radiation given once daily for 5 days for 7 weeks as part of CRT regimen.

Standard Treatment Cohort

Low Dose Radiation RADIATION

Radiation given once daily for 5 days for 6.5 weeks as part of CRT regimen.

De-Escalation CRT Cohort

Cisplatin DRUG

Given as part of CRT regimen (7 weekly doses). Investigator will choose the appropriate chemotherapy backbone to be given during CRT.

De-Escalation CRT Cohort; Standard Treatment Cohort

TFHX Regimen DRUG

Chemotherapy with paclitaxel, fluorouracil (5FU), and hydroxyurea given in combination with radiation therapy. Investigator will choose the appropriate chemotherapy backbone to be given during CRT.

Also known as: paclitaxel, fluorouracil (5-FU), hydroxyurea

De-Escalation CRT Cohort; Standard Treatment Cohort

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, human papillomavirus (HPV) negative head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, nasopharynx, larynx, or sinuses.
• Stage III or IV disease based on American Joint Committee on Cancer (AJCC) 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 1.1 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 core-needle or excisional biopsies will occur after baseline scans are performed and measurable lesions are identified. Fine-needle aspiration can be performed (i.e., to confirm extent of baseline lymph node involvement) following discussion with PI if not performed on a target lesion.
• 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) ≤ 2.5x upper limit of normal

You may not qualify if:

• Unequivocal demonstration of distant metastatic disease (M1 disease).
• Unidentifiable primary site.
• Intercurrent 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 cetuximab 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 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

RECRUITING

MeSH Terms

Interventions

Paclitaxel; Carboplatin; Cetuximab; Radiation; Cisplatin; Fluorouracil; Hydroxyurea

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Physical Phenomena; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Urea; Amides

Study Officials

• Ari Rosenberg, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Intake

CONTACT

1-855-702-8222; cancerclinicaltrials@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2023
• First Posted: August 22, 2023
• Study Start: December 18, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)