This phase I/II trial studies the side effects and the best dose of sorafenib tosylate and docetaxel when given together with cisplatin and to see how well they work in treating patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also help cisplatin and docetaxel work better by making tumor cells more sensitive to the drugs. Giving sorafenib tosylate, cisplatin, and docetaxel may be an effective treatment for squamous cell carcinoma of the head and neck.
PRIMARY OBJECTIVES: I. To define progression-free survival of patients with recurrent/metastatic squamous cell carcinoma treated with cisplatin/docetaxel/sorafenib (sorafenib tosylate) (CDS) combination chemotherapy. (Phase II) II. To determine the optimal doses of cisplatin/docetaxel/sorafenib to be used in the phase II portion of the trial. (Phase I) SECONDARY OBJECTIVES: I. To determine overall survival, response rate, conduct biomarker studies, toxicities. OUTLINE: This is a phase I, dose-escalation study of sorafenib tosylate and docetaxel followed by a phase II study. Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-14 of course 0. Beginning in course 1, patients receive sorafenib tosylate PO BID on days 1-21, docetaxel intravenously (IV) over 1 hour on day 1, and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive sorafenib tosylate PO BID in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Given daily PO in the a.m.
Given IV over 1 hour following Docetaxel administration
Given IV 1 hour prior to cisplatin administration
Correlative studies will be performed at the following time points. A total of three biopsies (blood and tumor samples) will be obtained in consenting patients.Pre-treatment biopsy to establish diagnosis and baseline data, Research biopsy obtained at the end of a two week period of sorafenib monotherapy just prior to administration of cycle1 with cisplatin and docetaxel, Research biopsy obtained at the end of two chemotherapy cycles.
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States
Incidence of dose-limiting toxicity (DLT) as graded according to the NCI-CTCAE v4.0 (Phase I)
A DLT will be considered a grade 3 non-hematologic toxicity or grade 4 hematologic toxicity that are probably or definitely related to treatment and result in treatment delay of more than 14 days.
Time frame: Day 21 of course 1
Progression-free survival (PFS) (Phase II)
PFS will be estimated using the Kaplan-Meier method.
Time frame: Time of enrollment to the date of progression diagnosis or death, assessed up to 4 weeks after completion of study treatment
Overall survival (OS)
OS will be estimated using the Kaplan-Meier method.
Time frame: Up to 4 weeks after completion of study treatment
Response rate evaluated by RECIST v1.1
Time frame: Up to 4 weeks after completion of study treatment
Biomarker levels
Biomarkers from tissue and blood samples will be evaluated and correlated with outcome parameters. Correlative biomarkers will be analyzed using mixed model for repeated measurement to account for the association of measures overtime from the same patient.
Time frame: Up to 42 days
Incidence of toxicities, graded according to NCI-CTCAE version 4.0
Time frame: Up to 4 weeks after completion of study treatment
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