Study of Sorafenib/Cetuximab in Head and Neck Cancer

NCT ID: NCT00815295

Last Updated: 2014-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2013-07-31

Brief Summary

In this Phase I B/II trial, we seek to determine the safety and efficacy of sorafenib with standard dose cetuximab in the treatment of patients with Recurrent and /or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN).

Detailed Description

This is a non-randomized phase I B/II trial enrolling 43 patients with recurrent and/or metastatic SCCHN who are not candidates for surgical salvage or definitive radiation. Subjects will receive Cetuximab and sorafenib until disease progression. Cetuximab will be given at standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib will be given 200 mg twice daily oral, continuous dosing to the 6 patients in cohort 1. If less than 3 patients experience dose limiting toxicities (DLT) at the 200mg BID dose, then 6 patients will be accrued at the 400mg BID dose level and toxicities will again be examined. Sorafenib will be given 400 mg twice daily oral, continuous dosing to the patients in cohort 2. One cycle equals 28 days. Tumor assessment will be performed every 8 weeks. Treatment continues until disease progression or unacceptable side effects.

Participating subjects will be asked to take part in an optional correlative study to provide previously archived diagnostic or therapeutic tumor samples obtained during the course of their routine medical care for their cancer of the head/neck. The optional tissue repository project is Duke University Health System (DUHS) Institutional Review Board (IRB) approved (eIRB # 11138 / "Tissue Acquisition Protocol for Analysis of Effects of Novel Chemotherapeutic Compounds). Subjects will be asked to sign a separate consent form to participate in the tissue collection study.

Conditions

Squamous Cell Cancer

Keywords

squamous cell cancer, head and neck

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab + sorafenib

Cetuximab will be given at standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib will be given at 200mg/m2 twice daily.

Group Type: EXPERIMENTAL

Sorafenib

Intervention Type: DRUG

Phase 1 - Dose level 1 : Sorafenib will be given 200 mg twice daily oral, Phase 1 - Dose level 2 : Sorafenib will be given 400 mg twice daily oral, Phase 2 : Sorafenib will be given at the maximum tolerated dose from Phase 1

Cetuximab

Intervention Type: DRUG

Cetuximab will be given at standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly.

Interventions

Sorafenib

Phase 1 - Dose level 1 : Sorafenib will be given 200 mg twice daily oral, Phase 1 - Dose level 2 : Sorafenib will be given 400 mg twice daily oral, Phase 2 : Sorafenib will be given at the maximum tolerated dose from Phase 1

Intervention Type: DRUG

Cetuximab

Cetuximab will be given at standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly.

Intervention Type: DRUG

Other Intervention Names

Nexavar; Erbitux

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed squamous cell carcinoma of the head and neck
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Age > 18 years old
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin > 9.0 g/dl
• Absolute neutrophil count (ANC) > 1,500/mm3
• Platelet count > 100,000/mm3
• Total bilirubin < 1.5 times upper limit of normal (ULN)
• Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 2.5 times the ULN ( < 5 x ULN for patients with liver involvement)
• Creatinine < 1.5 times ULN
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
• Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
• International normalized ratio (INR) < 1.5 or a Prothrombin Time / Partial thromboplastin time (PT/PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. - For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.

Exclusion Criteria

• Patients must not be candidates for potentially curative complete surgical resection or definitive radiation. (Patients may have received prior chemotherapy as part of definitive chemoradiotherapy and/or for recurrent/metastatic disease)
• Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Active clinically serious infection > Common Terminology Criteria for Adverse events (CTCAE) Grade 2.
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 (symptomatic and requiring medical intervention) within 4 weeks of first dose of study drug.
• Any other hemorrhage/bleeding event > CTCAE Grade 3 (bleeding requiring blood transfusion or intervention with endoscopy or surgery) within 4 weeks of first dose of study drug.
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of bleeding diathesis or coagulopathy Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
• Use of St. John's Wort or rifampin (rifampicin).
• Known or suspected allergy to sorafenib or any agent given in the this trial.
• Any malabsorption problem.
• Previous therapy with cetuximab for the treatment of recurrent and/or metastatic SCCHN. Previous therapy with cetuximab during definitive radiation therapy for locally advanced SCCHN is permitted so long as relapse of SCCHN occurred at least > 6 months (180 days) from the end of cetuximab therapy.
• Previous therapy with sorafenib, sunitinib or another small molecule known to inhibit the vascular endothelial growth factor receptors.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Neal Ready, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Locations

Duke University Health System

Durham, North Carolina, United States

Countries

United States

Other Identifiers

Pro00001516

Identifier Type: -

Identifier Source: org_study_id