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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00954278
First received: July 30, 2009
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

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 Intervention Phase
Carcinoma, Non Small Cell Lung
Drug: sorafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Toleration of dose escalation (dose-limiting toxicities) [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of sorafenib in dose-escalation (adverse events and serious adverse events) [ Time Frame: One year ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: July 2009
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sorafenib Drug: sorafenib
sorafenib (400mg or 600mg or 800mg) by mouth twice daily, for 28 days
Other Names:
  • BAY-439006
  • Nexavar

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00954278

Locations
United States, Wisconsin
University of Wisconsin - Madison
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
University of Wisconsin, Madison
Bayer
Investigators
Principal Investigator: Anne M Traynor, M.D. University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00954278     History of Changes
Other Study ID Numbers: H-2009-0011, CO 08511, IST 000381
Study First Received: July 30, 2009
Last Updated: March 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:
non small cell lung cancer
phase 1
sorafenib
intrapatient dose escalation

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 23, 2014