Sorafenib in Treating Patients With Advanced Malignant Solid Tumors - Full Text View

Sponsors and Collaborators:	University of California, Davis National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00810394

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 tosylate	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Sorafenib Sorafenib tosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Single Agent Sorafenib in Advanced Solid Tumors: Phase II Evaluation of Dose Re-Escalation Following a Dose Reduction (IST000375)

Further study details as provided by National Cancer Institute (NCI):

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 [ Designated as safety issue: Yes ]
Percentage of patients who are able to maintain an escalated dose of this drug for 28 days without dose interruption or de-escalation for toxicity after tolerating the initial dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response rates [ Designated as safety issue: No ]
Time to disease progression [ Designated as safety issue: No ]
Percentage of patients able to tolerate 2 successive dose escalations without a dose interruption or de-escalation for toxicity [ Designated as safety issue: Yes ]
Demographic and clinical characteristics of patients who are able to tolerate 2 successive dose escalations without a dose interruption [ Designated as safety issue: Yes ]

Estimated Enrollment:	51
Study Start Date:	December 2008
Estimated Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

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

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed malignant solid tumor
- Metastatic or unresectable disease
- Disease for which standard curative or palliative measures do not exist or are no longer effective, or solid tumor for which sorafenib tosylate is considered acceptable therapy
- Measurable or non-measurable disease
No symptomatic or uncontrolled brain metastasis
- Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis
- Previously treated brain metastases allowed provided the patient is neurologically stable and is off steroids and anticonvulsants

PATIENT CHARACTERISTICS:

Zubrod performance status 0-2
ANC ≥ 1,500/mm^3
Hemoglobin > 9.0 g/dL
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
Creatinine ≤ 1.5 times ULN
INR < 1.5 or PT/PTT within normal limits
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use adequate contraception prior to and during study treatment
- Men must use adequate contraception for ≥ 3 months following completion of treatment
No cardiac disease, including any of the following:
- NYHA class III-IV congestive heart failure
- Unstable angina (anginal symptoms at rest)
- New-onset angina (beginning within the past 3 months)
- Myocardial infarction within the past 6 months
No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
No uncontrolled hypertension defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management
No thrombolic or embolic events (e.g., cerebrovascular accident including transient ischemic attacks) within the past 6 months
No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within the past 4 weeks
No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks
No evidence or history of bleeding diathesis or coagulopathy
No serious non-healing wound, ulcer, or bone fracture
No active clinically serious infection > CTCAE grade 2
No known HIV infection or chronic hepatitis B or C
No known or suspected allergy to sorafenib tosylate or any agent given in the course of this study
No condition that impairs the ability to swallow whole pills
No significant malabsorption problem
No significant traumatic injury in the past 4 weeks

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior sorafenib tosylate or sunitinib
Recovered from all side effects of previous therapy (except for alopecia, lymphopenia, and hyperglycemia) to ≤ grade 1
At least 3 months since prior therapy with bevacizumab
At least 4 weeks since prior major surgery or open biopsy
At least 2 weeks since prior chemotherapy, immunotherapy, targeted therapy, or radiotherapy
No concurrent St. John's wort or rifampin (rifampicin)

Contacts and Locations

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

Locations

United States, California
University of California Davis Cancer Center	Recruiting
Sacramento, California, United States, 95817
Contact: Clinical Trials Office - University of California Davis Cancer 916-734-3089

Sponsors and Collaborators

University of California, Davis

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Primo N. Lara, MD

University of California, Davis

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of California Davis Cancer Center ( Primo N. Lara )
Study ID Numbers:	CDR0000628775, UCDCC-213, 200816532-1, BAYER-UCDCC-213
Study First Received:	December 17, 2008
Last Updated:	January 21, 2009
ClinicalTrials.gov Identifier:	NCT00810394 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Protein Kinase Inhibitors
Sorafenib

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

Protein Kinase Inhibitors
Sorafenib
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 07, 2009