Intra-patient Dose Escalation Study of Sorafenib in Advanced Non-small Cell Lung Cancer

Sponsor

University of Wisconsin, Madison (Other)

Overall Status

Completed

CT.gov ID

NCT00954278

Collaborator

Bayer (Industry)

Enrollment

Location

Arm

76.8

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the number of patients with advanced, relapsed non-small cell lung cancer who can tolerate dose escalation sorafenib from 400 mg twice daily to either 600 mg twice daily or 800 mg twice daily. Safety and tolerability of sorafenib will also be examined.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non Small Cell Lung	Drug: sorafenib	Phase 1

Detailed Description

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality in the U.S. Time to progression in advanced disease remains poor and further study of newer agents with novel mechanisms of action is needed to improve duration and quality of life for NSCLC patients.

Sorafenib is an oral-multi-kinase inhibitor with effects on tumor proliferation and tumor angiogenesis. Sorafenib has demonstrated activity in preclinical models of NSCLC both in combination with chemotherapy and as monotherapy. A recent intra-patient dose escalation trial of sorafenib in renal cell carcinoma showed positive response rates and tolerability up to 1200mg in 91% of patients.

This study attempts a similar dose-escalation of sorafenib in NSCLC patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I, Intrapatient Dose-Escalation Study of Sorafenib in Advanced or Relapsed Non-Small Cell Lung Cancer (NSCLC)

Actual Study Start Date :

Jul 28, 2009

Actual Primary Completion Date :

Dec 23, 2015

Actual Study Completion Date :

Dec 23, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: sorafenib	Drug: sorafenib sorafenib (400mg or 600mg or 800mg) by mouth twice daily, for 28 days Other Names: BAY-439006 Nexavar

Arm

Intervention/Treatment

Experimental: sorafenib

Drug: sorafenib

sorafenib (400mg or 600mg or 800mg) by mouth twice daily, for 28 days

Other Names:

BAY-439006

Nexavar

Outcome Measures

Primary Outcome Measures

Toleration of dose escalation (dose-limiting toxicities) [One year]

Secondary Outcome Measures

Safety of sorafenib in dose-escalation (adverse events and serious adverse events) [One year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed, advanced (stage IIIB with pleural effusion, stage IV, or recurrent), kras mutation positive, non-small cell lung cancer (NSCLC)
Measurable disease per RECIST criteria
Patients must have received one + prior chemotherapy regimens for NSCLC
Patients may have treated and clinically stable brain metastases
Adequate bone marrow, liver and renal function
Women of childbearing potential must have a negative serum pregnancy test 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, and for 3 months after last administration of sorafenib
Patients must have the ability to understand and willingness to sign a written informed consent
International normalized ratio(INR) < 1.5 or prothrombin time/ partial thromboplastin time (PT/PTT) within normal limits

Exclusion Criteria:

Prior exposure to a Ras pathway inhibitor
Any other anti-tumor therapy within 3 weeks of enrollment
Prior bevacizumab within the past 6 weeks
An active secondary malignancy except non-melanoma skin cancer
Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina or new onset angina or myocardial infarction within the past 6 months
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
Uncontrolled hypertension, defined as systolic blood pressure > 150mm Hg or diastolic pressure > 90mm Hg, despite optical 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 cerebrovascular accident including transient ischemic attack within the past 6 months
Pulmonary hemorrhage/bleeding event >/= CTCAE Grade 2 within 4 weeks of first dose of study drug
Any other hemorrhage/bleeding event >/= CTCAE Grade 3 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
Known or suspected allergy to sorafenib or any agent given in the course of the trial
Any condition that impairs patient's ability to swallow whole pills
Any malabsorption problem