Pilot Study of Induction Therapy Followed by Response-adaptive Treatment and Dynamic Changes in Circulating Tumor DNA in Locoregionally Advanced HPV Negative Head and Neck Squamous Cell Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Paclitaxel
- Conditions
- HPV-Negative Squamous Cell Carcinoma
- Sponsor
- University of Chicago
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Percentage of participants that complete study treatment and provide all required research blood draws.
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Induction Treatment Arm
All participants will receive 3 cycles (9 weeks) of chemotherapy with paclitaxel, carboplatin, and cetuximab.
Intervention: Paclitaxel
Induction Treatment Arm
All participants will receive 3 cycles (9 weeks) of chemotherapy with paclitaxel, carboplatin, and cetuximab.
Intervention: Carboplatin
Induction Treatment Arm
All participants will receive 3 cycles (9 weeks) of chemotherapy with paclitaxel, carboplatin, and cetuximab.
Intervention: Cetuximab
De-Escalation CRT Cohort
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.
Intervention: Low Dose Radiation
De-Escalation CRT Cohort
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.
Intervention: Cisplatin
De-Escalation CRT Cohort
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.
Intervention: TFHX Regimen
Standard Treatment Cohort
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.
Intervention: Standard Dose Radiation
Standard Treatment Cohort
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.
Intervention: Cisplatin
Standard Treatment Cohort
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.
Intervention: TFHX Regimen
Outcomes
Primary Outcomes
Percentage of participants that complete study treatment and provide all required research blood draws.
Time Frame: To be measured at end of treatment period (9 weeks)
Determine if ctDNA levels is predicative of disease response
Time Frame: To be measured at end of treatment period (9 weeks)
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.
Secondary Outcomes
- 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)