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Sorafenib in Treating Patients With Advanced Malignant Solid Tumors

This study has been completed.
Information provided by (Responsible Party):
University of California, Davis Identifier:
First received: December 17, 2008
Last updated: March 20, 2017
Last verified: March 2017

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: Intervention Model: Single Group Assignment
Masking: No masking
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 Tolerating Re-escalated Dose of Sorafenib for 28 Days Without Dose Interruption or De-escalation for Toxicity [ Time Frame: At least 3 months ]
    Overall percentage of patients tolerating a dose escalation to 600 mg twice daily for 28 days plus the percentage tolerating a re-escalation to 400 mg twice daily in Cycle 3.

Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: At least 3 months ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR).

  • Time to Disease Progression [ Time Frame: Up to 2 years ]
    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Enrollment: 50
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:



  • 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.


  • 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.


  • 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.
  • 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  • 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.
  • International normalized ratio < 1.5 or a Prothrombin Time/Partial thromboplastin time within normal limits.

Exclusion Criteria

  • Prior therapy with sorafenib or sunitinib.
  • Cardiac disease: Congestive heart failure > class II New York Heart Association.
  • 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.
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Please refer to this study by its identifier: NCT00810394

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

Responsible Party: University of California, Davis Identifier: NCT00810394     History of Changes
Other Study ID Numbers: UCDCC#213
UCDCC-213 ( Other Identifier: University of California Davis )
IST000375 ( Other Grant/Funding Number: Bayer )
Study First Received: December 17, 2008
Results First Received: January 19, 2017
Last Updated: March 20, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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

Additional relevant MeSH terms:
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs processed this record on May 25, 2017