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Sorafenib and Bortezomib in Treating Patients With Advanced Cancer
This study is currently recruiting participants.
Study NCT00303797   Information provided by National Cancer Institute (NCI)
First Received: March 15, 2006   Last Updated: August 4, 2009   History of Changes

March 15, 2006
August 4, 2009
December 2005
December 2006   (final data collection date for primary outcome measure)
 
 
Complete list of historical versions of study NCT00303797 on ClinicalTrials.gov Archive Site
 
 
 
Sorafenib and Bortezomib in Treating Patients With Advanced Cancer
A Phase I Study of the Raf Kinase/VEGFR Inhibitor BAY 43-9006 in Combination With the Proteasome Inhibitor PS-341 in Patients With Advanced Malignancies

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

PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib and bortezomib in treating patients with advanced cancer.

OBJECTIVES:

  • Determine the maximum tolerated dose of sorafenib and bortezomib in patients with advanced malignancies.
  • Describe the toxicities associated with the combination of sorafenib and bortezomib.
  • Evaluate the therapeutic antitumor activity of the combination of sorafenib and bortezomib.
  • Evaluate the effects of sorafenib on the disposition of bortezomib.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 groups according to disease type.

  • Group I (solid tumors-dose-escalation group): Patients receive oral sorafenib twice daily on days 1-21 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sorafenib and bortezomib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Group II (multiple myeloma or chronic lymphocytic leukemia-maximum tolerated dose [MTD] group): Patients receive oral sorafenib at the MTD twice daily on days 3-21 of course 1 and on days 1-21 of each subsequent course. Patients also receive bortezomib IV over 3-5 seconds at the MTD on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 3 months.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Phase I
Interventional
Treatment
  • Leukemia
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: bortezomib
  • Drug: sorafenib tosylate
 
 

*   Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
 
Recruiting
50
 
December 2006   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Cytologically or histologically proven unresectable solid tumor for which no curative treatment options exist (group I - dose-escalation phase)
    • Multiple myeloma or chronic lymphocytic leukemia requiring treatment (group II - maximum tolerated dose phase)

      • Failed ≥ 1 prior regimen
      • Non-secretory myeloma allowed
  • No known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
  • Tumor amenable to serial sampling (group II)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Platelet count ≥ 100,000/mm^3 (75,000/mm^3 for patients with multiple myeloma [group II])
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN (5 times ULN if liver involvement)
  • Creatinine ≤ 1.5 times ULN (2.5 times ULN for patients with multiple myeloma [group II])
  • Life expectancy ≥ 12 weeks
  • No uncontrolled infection
  • No New York Heart Association class III or IV heart disease
  • No uncontrolled hypertension, labile hypertension, or history of poor compliance with antihypertensive medication
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No sensory peripheral neuropathy of any etiology > grade 1 or neuropathic pain of any etiology
  • No active HIV infection requiring therapy
  • No inability to swallow that would preclude use of oral medications
  • No evidence of bleeding diathesis
  • Medically capable and willing to provide biologic specimens as required (mandatory for patients in group II)

PRIOR CONCURRENT THERAPY:

  • Prior bortezomib allowed
  • More than 3 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas) and recovered
  • More than 4 weeks since prior immunotherapy or biologic therapy
  • More than 2 weeks since prior steroid therapy (group II only)
  • No prior anti-vascular endothelial growth factor therapy
  • More than 4 weeks since prior full-field radiotherapy (2 weeks for limited-field radiotherapy)
  • No prior radiation to > 25% of bone marrow
  • More than 4 weeks since major surgery (e.g., laparotomy) (2 weeks for minor surgery)

    • Insertion of a vascular access device is not considered major or minor surgery
  • No concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary other therapy considered investigational
  • No concurrent prophylactic colony-stimulating factors
  • No concurrent therapeutic anticoagulation

    • Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided requirements for PT, INR, or PTT are met
  • No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, and phenobarbital), rifampin, or Hypericum perforatum (St. John's Wort)
  • No concurrent participation in any other study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy), either for symptom control, or therapeutic intent
Both
18 Years and older
No
 
United States
 
NCT00303797
 
CDR0000458075, MAYO-MC0511, NCI-7082
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Shaji K. Kumar, MD Mayo Clinic
Investigator: Neil E. Kay, MD Mayo Clinic
National Cancer Institute (NCI)
August 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP