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Sorafenib and Bortezomib in Treating Patients With Advanced Cancer
This study has been completed.

First Received on March 15, 2006.   Last Updated on June 19, 2010   History of Changes
Sponsor: Mayo Clinic
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00303797
  Purpose

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.


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

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Estimated Enrollment: 50
Study Start Date: December 2005
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00303797

Locations
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Shaji K. Kumar, MD Mayo Clinic
Investigator: Neil E. Kay, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00303797     History of Changes
Other Study ID Numbers: CDR0000458075, MAYO-MC0511, NCI-7082
Study First Received: March 15, 2006
Last Updated: June 19, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
stage IV chronic lymphocytic leukemia
stage III multiple myeloma
refractory multiple myeloma
refractory chronic lymphocytic leukemia

Additional relevant MeSH terms:
Neoplasms
Leukemia
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012