Study of Sorafenib/Cetuximab in Head and Neck Cancer

NCT00815295 | Completed Phase 1 Results DMC

• 1 other identifier: Pro00001516
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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).

Conditions

Squamous Cell Cancer

Keywords

squamous cell cancer, head and neck

Outcome Measures

Primary Outcomes (2)

• Phase 1 - Maximum Tolerated Dose (MTD) of Sorafenib Administered With Cetuximab (400 mg/m2 Loading Dose Followed by 250 mg/m2 Weekly)

  The MTD is based upon dose-limiting (DLTs) experienced during Cycle 1 of treatment. The MTD is the maximum dose level at which 0/6 or 1/6 patients experience DLT. Using Common Toxicity Criteria for Adverse EVents (CTCAE) version 3.0, DLTs are defined as any Grade 4 hematologic toxicity, or Grade 3 or 4 non-hematologic toxicity. A DLT will not be considered to have occurred in the case of a grade 3 or 4 allergic reaction due to cetuximab.

  Cycle 1 (28 Days)

• Tumor Control Rate

  The proportion of patients for whom the best overall response is complete response (CR), partial response (PR) or stable disease (SD). A CR occurs when all lesions disappear; whereas, a PR is indicated when there is at least a 30% decrease in the sum of the longest diameters (LD) of the target lesion. A PD (progressive disease) occurs when there is at least a 20% increase in the sum of the LD relative to the smallest sum LD recorded since treatment is initiated. Disease is considered stable if there is no response and no PD. If follow-up assessments are not available, the best overall response is unevaluable.

  1 year

Secondary Outcomes (3)

• Median Survival

  5 years

• Median Progression-Free Survival (PFS)

  5 years

• Phase 2 - Mean Change From Baseline in Quality of Life - Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N)

  5 years

Study Arms (1)

Cetuximab + sorafenib

EXPERIMENTAL

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.

Drug: Sorafenib; Drug: Cetuximab

Interventions

Sorafenib 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

Also known as: Nexavar

Cetuximab + sorafenib

Cetuximab DRUG

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

Also known as: Erbitux

Cetuximab + sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead
• Bayer: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Neoplasms, Squamous Cell

Interventions

Sorafenib; Cetuximab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Neal Ready, MD
• Organization: Duke University Medical Center

neal.ready@duke.edu

919-668-6688

Study Officials

• Neal Ready, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2008
• First Posted: December 30, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: December 8, 2014
• Results First Posted: December 8, 2014

Record last verified: 2014-12

Locations

US (1)