A Randomized, Phase II Study of Definitive Radiotherapy With Concurrent Cisplatin vs. Docetaxel-cetuximab in Locally Advanced Head and Neck Squamous Cell Carcinoma: an ERCC1 Biomarker Enrichment and Interaction Design
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel
- Conditions
- Squamous Cell Carcinoma
- Sponsor
- Christopher Wilke
- Enrollment
- 120
- Locations
- 2
- Primary Endpoint
- Time To Progression (TTP)
- Status
- Recruiting
- Last Updated
- 16 days ago
Overview
Brief Summary
The goal of this clinical research study is to learn which chemotherapy combination may be more effective in treating locally advanced head and neck squamous cell carcinoma (HNSCC). The side effects of these combinations will also be studied.
This study treatment consists of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. For study chemotherapy, patients will be randomized between cisplatin or the combination of docetaxel and cetuximab. Subjects will be stratified depending on HPV status and the presence of ERCC-1 [4F9] in the tumor prior to randomization. The study will evaluate cisplatin vs. docetaxel-cetuximab in the overall population, and test which radiation and chemotherapy combination works best in relationship to how much ERCC-1 [4F9] is expressed in a tumor.
Detailed Description
If randomized to the cisplatin arm, patients receive cisplatin, 40 mg/m2, administered intravenously (IV) once a week (+/- 2 days) for 7 weeks. Per investigator discretion, if radiation continues beyond 7 weeks due to technical factors (not toxicity delays), an 8th dose of concurrent cisplatin may be added. Cisplatin can be given either before or after the radiation therapy fraction that is given on the same day. If a dose of cisplatin is omitted when radiotherapy is ongoing, it will not be made up or added to the end of treatment. The omitted dose and the reason for the omission should be recorded in the site's source documentation. If radiotherapy is held, cisplatin should be held during the treatment break and resumed when radiation restarts. Patients randomized to Cetuximab arm receive cetuximab, 250 mg/m2, IV over 60 minutes on a weekly schedule (+/- 2 days). . Cetuximab may be administered either before or after the radiation fraction that is given on the same day. Docetaxel will be administered at least 30 minutes following cetuximab. It is not permitted to make up missed doses of cetuximab or docetaxel. If a radiation therapy treatment break occurs, cetuximab should be held. When radiation restarts, cetuximab should resume. Cetuximab will be given once a week (+/- 2 days) for a total of 7 doses concurrent with radiation therapy and docetaxel.
Investigators
Christopher Wilke
Radiation Oncologist
University of Pittsburgh
Eligibility Criteria
Inclusion Criteria
- •Pathologically confirmed squamous cell carcinoma, undifferentiated carcinoma, or poorly differentiated carcinoma of the oropharynx, larynx, or hypopharynx with no evidence of distant metastasis. Biopsy sampling of primary tumor with pathology report documenting diagnostic tissue type is required.
- •Patients must have stage III, IVa or IVb disease as determined by imaging studies and complete head and neck exam. Staging evaluation should be in accordance with the American Joint Committee on Cancer Staging Manual, 7th edition.
- •Patients with oropharyngeal squamous cell carcinoma may have p16(+) or p16(-) disease; in these patients, p16 status must be known prior to randomization. Assessment of p16 status may occur locally or centrally. Note: The definition of p16(+) disease is diffuse nuclear and cytoplasmic staining in ≥ 70% of tumor cells.
- •Patients must be untreated with curative-intent surgery for current diagnosis of Stage III, IVa, or IVb disease. Diagnostic biopsy of primary tumor and/or nodal sites is permitted.
- •Diagnostic simple tonsillectomy is permitted, provided patient has RECIST-measurable residual tumor and/or nodal disease.
- •Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy/radiotherapy), and has not recurred.
- •Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible.
- •No prior systemic treatment (chemotherapy or biologic/molecular targeted therapy) or radiation treatment for head and neck cancer.
- •Patients may have received chemotherapy or radiation for a previous, curatively treated non-HNSCC malignancy, provided at least 2 years have elapsed.
- •Patients must be untreated with radiation above the clavicles.
Exclusion Criteria
- Not provided
Arms & Interventions
Docetaxel-Cetuximab-IMRT
Docetaxel 15 mg/m2 weekly x 7; Cetuximab 400 mg/m2 load, one week prior to IMRT; Cetuximab 250 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)
Intervention: Docetaxel
Docetaxel-Cetuximab-IMRT
Docetaxel 15 mg/m2 weekly x 7; Cetuximab 400 mg/m2 load, one week prior to IMRT; Cetuximab 250 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)
Intervention: IMRT
Cisplatin-IMRT
Cisplatin 40 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)
Intervention: IMRT
Cisplatin-IMRT
Cisplatin 40 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)
Intervention: Cisplatin
Docetaxel-Cetuximab-IMRT
Docetaxel 15 mg/m2 weekly x 7; Cetuximab 400 mg/m2 load, one week prior to IMRT; Cetuximab 250 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)
Intervention: Cetuximab
Outcomes
Primary Outcomes
Time To Progression (TTP)
Time Frame: Up to 5 years
Time To Progression is the duration of time from date of study entry until the first appearance of new metastatic lesions or objective tumor progression in patients with increased tumoral ERCC1 expression. Progression is defined per RECIST v1.1 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Secondary Outcomes
- Time to progression (TTP)(Up to 5 years)
- Local Control Rate (LRC)(Up to 5 years)
- Rate of distant metastases(Up to 5 years)
- Validation candidate cutpoint(Up to 5 years)
- Response per RECIST 1.1(Up to 5 years)
- 2-year (Time to Progression) TTP(At 2 years)
- FACT-H&N FACT - Head & Neck(Up to 2 years)
- Functional Assessment of Cancer Therapy (FACT-Cog)(Up to 2 years)
- Patient Health Questionnaire (PHQ-9)(Up to 2 years)
- General Anxiety Disorder-7 (GAD-7)(Up to 2 years)
- Modified Edmonton Symptom Assessment System (MESAS)(Up to 2 years)
- Impact of Events Scale - Intrusion (IES-I)(Up to 2 years)
- Disease Related Blame Scale (DBS)(Up to 2 years)
- Perceived Threat Scale (PTS)(Up to 2 years)
- The Brief Pain Inventory(Up to 2 years)