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Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function
This study is ongoing, but not recruiting participants.
First Received: July 8, 2005   Last Updated: March 25, 2009   History of Changes
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00118170
  Purpose

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

Sorafenib may have different effects in patients who have changes in their liver or kidney function.

PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib in treating patients with metastatic or unresectable solid tumors, multiple myeloma, or non-Hodgkin's lymphoma with or without impaired liver or kidney function.


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

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Lymphoma Multiple Myeloma
Drug Information available for: Sorafenib Sorafenib tosylate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Pharmacokinetic and Phase I Study of Sorafenib (BAY 43-9006, NSC 724772, IND 69896) For Solid Tumors and Hematologic Malignancies in Patients With Hepatic or Renal Dysfunction

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

Primary Outcome Measures:
  • Pharmacokinetics (part 1) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tolerable starting dose (part 2) [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: October 2004
Detailed Description:

OBJECTIVES:

  • Determine the pharmacokinetics of sorafenib in patients with metastatic or unresectable solid tumors, multiple myeloma, or non-Hodgkin's lymphoma with or without hepatic or renal dysfunction.
  • Determine the maximum tolerated dose of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 9 treatment cohorts according to hepatic or renal function.

Patients receive oral sorafenib once on day 1 and then once daily, twice daily, or every other day beginning on day 8 and continuing for 3 months.

Patients are re-evaluated at 3 months. Patients with responding disease may continue study treatment in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients (per treatment cohort) receive escalating doses of sorafenib until the maximum tolerated dose (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. At least 6 patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 120 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:

  • Histologically or cytologically confirmed solid tumor, multiple myeloma, or non-Hodgkin's lymphoma

    • Metastatic or unresectable disease
  • Standard curative or palliative measures do not exist OR are no longer effective
  • Measurable or non-measurable disease

    • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
    • The following are considered nonmeasurable disease:

      • Bone lesions
      • Ascites
      • Pleural or pericardial effusion
      • Lymphangitis cutis or pulmonis
      • Abdominal masses that are not confirmed and followed by imaging techniques
      • Cystic lesions
  • Hepatic or renal function meeting 1 of the following criteria*:

    • Bilirubin normal AND SGOT normal AND creatinine clearance ≥ 60 mL/min (cohort 1)
    • Bilirubin > upper limit of normal (ULN) but ≤ 1.5 times ULN AND/OR SGOT > ULN (cohort 2)
    • Creatinine clearance > 40 mL/min but < 59 mL/min (cohort 3)
    • Bilirubin > 1.5 times ULN but ≤ 3 times ULN AND any SGOT (cohort 4)
    • Creatinine clearance > 20 mL/min but < 39 mL/min (cohort 5)
    • Bilirubin > 3 times ULN but ≤ 10 times ULN AND any SGOT (cohort 6)
    • Creatinine clearance < 20 mL/min (cohort 7)
    • Albumin < 2.5 g/dL AND any bilirubin AND any SGOT (cohort 8)
    • Requires hemodialysis AND any creatinine clearance (cohort 9) NOTE: *Patients meeting criteria for > 1 cohort (e.g., elevated bilirubin AND reduced creatinine clearance) are only eligible for enrollment into cohort 8
  • Brain metastases allowed provided all of the following criteria are met:

    • Patient is asymptomatic
    • Disease was previously treated
    • Patient is not currently receiving steroid therapy
    • Disease is radiographically stable for ≥ 2 months

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 75,000/mm^3
  • No evidence of bleeding diathesis

Hepatic

  • See Disease Characteristics
  • No evidence of biliary obstruction

    • Prior treatment with stents or drains for biliary obstruction allowed provided patient has been observed for ≥ 1 week after treatment AND organ dysfunction has stabilized

Renal

  • See Disease Characteristics
  • No evidence of renal obstruction

    • Prior treatment with stents or drains for renal obstruction allowed provided patient has been observed for ≥ 1 week after treatment AND organ dysfunction has stabilized

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No uncontrolled hypertension

Gastrointestinal

  • No GI disease resulting in an inability to take oral medication
  • No requirement for IV alimentation
  • No active peptic ulcer disease

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No AIDS
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, melphalan, or mitomycin)

Endocrine therapy

  • See Disease Characteristics
  • No concurrent steroids

Radiotherapy

  • At least 4 weeks since prior radiotherapy

Surgery

  • At least 4 weeks since prior major surgery
  • No prior surgical procedures affecting gastrointestinal (GI) absorption

Other

  • No concurrent medications known to cause hepatic or renal toxicity (e.g., antiseizure medications or non-steroidal anti-inflammatory agents)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No concurrent therapeutic anticoagulation

    • 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, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00118170

Locations
United States, California
Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Veterans Affairs Medical Center - San Diego
San Diego, California, United States, 92161
United States, Connecticut
Norwalk Hospital
Norwalk, Connecticut, United States, 06856
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
Columbus, Ohio, United States, 43210-1240
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Antonius A. Miller, MD Wake Forest University
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000433342, CALGB-60301
Study First Received: July 8, 2005
Last Updated: March 25, 2009
ClinicalTrials.gov Identifier: NCT00118170     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
stage III multiple myeloma
recurrent adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
recurrent adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma
recurrent mantle cell lymphoma
Waldenstrom macroglobulinemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
splenic marginal zone lymphoma

Study placed in the following topic categories:
Blood Protein Disorders
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Mantle Cell Lymphoma
Lymphoma, B-Cell, Marginal Zone
Paraproteinemias
Hemostatic Disorders
Protein Kinase Inhibitors
Lymphoblastic Lymphoma
Follicular Lymphoma
Lymphoma, Large-cell, Immunoblastic
Lymphoma, Small Cleaved-cell, Diffuse
Lymphoma, B-Cell
Hemorrhagic Disorders
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Large-cell
Leukemia, B-cell, Chronic
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphomatoid Granulomatosis
Immunoproliferative Disorders
Hematologic Diseases
Blood Coagulation Disorders
Vascular Diseases
Recurrence
Multiple Myeloma
Burkitt's Lymphoma
Lymphatic Diseases
Chronic Lymphocytic Leukemia

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

ClinicalTrials.gov processed this record on May 07, 2009