Sorafenib in Treating Patients With Advanced Malignant Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT00810394
First received: December 17, 2008
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying the side effects and best dose of sorafenib and to see how well it works in treating patients with advanced malignant solid tumors.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Single Agent Sorafenib in Advanced Solid Tumors: Phase II Evaluation of Dose Re-Escalation Following a Dose Reduction (IST000375)

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Percentage of patients who are able to maintain a re-escalated dose of sorafenib tosylate for 28 days without dose interruption or de-escalation for toxicity [ Time Frame: At least 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rates [ Time Frame: At least 3 months ] [ Designated as safety issue: No ]
    Percentage of patients whose cancer shrinks or disappears after treatment

  • Time to disease progression [ Time Frame: time after a disease is diagnosed until the disease starts to get worse ] [ Designated as safety issue: No ]
  • Percentage of patients able to tolerate 2 successive dose escalations without a dose interruption or de-escalation for toxicity [ Time Frame: At least 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 51
Study Start Date: December 2008
Study Completion Date: March 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib
Dose Re-Escalation Following a Dose Reduction
Drug: Sorafenib
Patients will be registered and started on the standard recommended dose-schedule for sorafenib (400 mg tablet by mouth twice a day continuously). Dose reductions will be instituted in the event of grade 3 or higher hematologic or non-hematologic toxicity or for any toxicity that is considered by the patient or physician as intolerable.
Other Name: Nexavar

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the feasibility of re-escalating the dose of sorafenib tosylate in patients with advanced malignant solid tumors who initially required a dose reduction for toxicity, and dose escalation in those patients who are able to tolerate the initial dose.

Secondary

  • To evaluate the efficacy of this drug in these patients who are able to tolerate a dose escalation initially or after a dose reduction compared to those who are unable to tolerate a dose escalation.

Tertiary

  • To evaluate the percentage and demographic characteristics of patients who are able to tolerate 2 dose escalations without a dose reduction.

OUTLINE: This is a dose-finding study.

  • Course 1: Patients receive oral sorafenib tosylate twice daily at dose level 0 on weeks 1-4.
  • Course 2: Patients experiencing no dose-limiting or intolerable toxicities receive oral sorafenib tosylate at dose level +1 twice daily on weeks 5-8; while patients experiencing dose-limiting or intolerable toxicities receive oral sorafenib tosylate at dose level -1 once daily on weeks 5-8.
  • Course 3: Depending on whether or not patients are experiencing dose-limiting or intolerable toxicities, they are escalated to dose level 0 or dose level +2 (patients in both dose levels receive oral sorafenib tosylate twice daily) in weeks 9-12, or de-escalated to dose level 0 or dose level -2 (patients in dose level -2 receives oral sorafenib tosylate once every other day) in weeks 9-12.
  • Maintenance therapy: Patients receive oral sorafenib tosylate at the dose level* attained at the end of course 3. Treatment continues in the absence of unacceptable toxicity.

NOTE: *Dose level de-escalation for toxicity or dose re-escalation after a toxicity-related dose reduction allowed to a maximum level of the initial dose level of the maintenance therapy.

After completion of study therapy, patients are followed for up to 1 year.

  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 metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective or solid tumor for which sorafenib is considered acceptable therapy
  • Age > 18 years old
  • Zubrod Performance Status 0 - 2
  • Measurable or non-measurable disease.
  • Adequate bone marrow, liver and renal function
  • Any number of prior chemotherapy regimens are allowed.
  • Any prior chemotherapy, immunotherapy or targeted therapy must have been completed at least 2 weeks prior to start of this protocol and all side effects resolved to grade 1 or less. Any prior radiation must have been completed at least 2 weeks prior to start of therapy.
  • Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment
  • Women of childbearing potential and men must agree to use adequate contraception 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.
  • Ability to understand and the willingness to sign a written informed consent.
  • INR < 1.5 or a PT/PTT within normal limits.

Exclusion Criteria

  • Prior therapy with sorafenib or sunitinib.
  • Cardiac disease: Congestive heart failure > class II NYHA.
  • Symptomatic or uncontrolled brain metastasis.
  • No component of squamous carcinoma can be present in any patient with non-small cell lung cancer
  • 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 HIV infection or chronic Hepatitis B or C.
  • Active clinically serious infection > 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 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 dose of study drug.
  • Use of St. John's Wort or rifampin
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • Any condition that impairs patient's ability to swallow whole pills.
  • Any significant malabsorption problem.
  • Therapy with bevacizumab < 3 months prior to first dose of study drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00810394

Locations
United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Bayer
Investigators
Principal Investigator: Primo N. Lara, MD University of California, Davis
  More Information

Additional Information:
No publications provided by University of California, Davis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT00810394     History of Changes
Other Study ID Numbers: CDR0000628775, UCDCC-213, IST000375
Study First Received: December 17, 2008
Last Updated: June 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Davis:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014