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Sorafenib in Treating Patients With Relapsed or Refractory Multiple Myeloma

Primary Purpose

Refractory Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
sorafenib tosylate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have a confirmed diagnosis of previously treated, active multiple myeloma, with measurable disease present to evaluate response; all tests for establishing baseline disease status (serum protein electrophoresis, urine protein electrophoresis and bone marrow biopsy) must be performed within 28 days prior to registration and MUST be documented on the Baseline and Follow-up Tumor Assessment Form for Multiple Myeloma Patients must have relapsed or resistant disease, defined as relapsing after autologous stem cell transplantation or is either relapsing or is resistant after >= 1 line of prior therapy for myeloma; a minimum of 42 days must have elapsed since prior transplant Relapse: is defined as the occurrence of any of the following during or after previous treatment: A myeloma protein increase by more than 100% from the lowest previously recorded level A myeloma protein increase above the response criteria for PR Reappearance of any myeloma peak that had disappeared during the previous treatment Increase in the size and number of lytic bone lesions and/or focal lesions recognized in radiographic studies (x-ray, MRI, PET and/or CT scans) Resistant disease: is defined as disease not responding (i.e. not achieving CR, R, PR) to previous therapy Patients must be off myelosuppressive chemotherapy for >= 21 days (>= 6 weeks for nitrosoureas) and non-myelosuppressive chemotherapy and XRT for >= 14 days and recovered from all treatment associated toxicities prior to registration Patients must have a Zubrod Performance Status (PS) of 0-2 Patients must have received no prior treatment with BAY 43-9006 Patients must have currently have no significant neurotoxicity, defined as Grade >= 2 neurotoxicity per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Patients must have no evidence of POEMS (polyneuropathy, organomegaly, endocrinopathy, presence of M-protein, and skin changes) Syndrome There must be no active infection requiring antibiotics Bilirubin =< 1.5 times the institutional upper limit of normal (IULN) AST (SGOT or SGPT) =< 5 times the institutional upper limit of normal (IULN) Serum creatinine =< the institutional upper limit of normal (IULN) ANC > 750/ul Platelet count > 75,000/ul Patients must be able to take oral medication without crushing, dissolving or chewing tablets Patients must not be taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, and phenobarbital), rifampin, or St. John's Wort Patients must not have a significant history of cardiac disease, e.g., uncontrolled hypertension, unstable angina, congestive-heart failure, and myocardial infarction within the last six months, or cardiac ventricular arrhythmias requiring medication Patients must not have any evidence of bleeding diathesis, uncontrolled diabetes mellitus, or other serious or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol Patients must not be on therapeutic anticoagulation No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years Pregnant or nursing women may not participate in this trial because of increased risk of fetal harm including fetal death from the chemotherapeutic agents; women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method Institutions must have IRB approval of S0309 ("Myeloma Specimen Repository Protocol, Ancillary"); patients must be offered participation in S0309; with the patient's consent, bone marrow aspirates and serum specimens will be submitted for testing via S0309; patients must be registered separately to S0309 in order for institutions to receive credit for specimen submission to S0309; NOTE: immediately following S0434 registration, the CRA will need to have completed the S0309 Registration Form and eligibility worksheet in hand for use All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Sites / Locations

  • Southwest Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (sorafenib tosylate)

Arm Description

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Overall response rate (confirmed CR, R and PR)
Incidence of qualitative and quantitative toxicities associated with this regimen
Overall survival
Progression-free survival

Secondary Outcome Measures

Full Information

First Posted
November 11, 2005
Last Updated
January 4, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00253578
Brief Title
Sorafenib in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official Title
A Phase II Trial of BAY 43-9006 (Sorafenib) (NSC-724772) in Patients With Relapsing or Resistant Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial is studying how well sorafenib works in treating patients with relapsed or refractory multiple myeloma. 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
Detailed Description
PRIMARY OBJECTIVES: I. To assess the overall response rate (confirmed CR, R and PR) in patients with relapsed/refractory multiple myeloma treated with BAY 43-9006. II. To evaluate qualitative and quantitative toxicities associated with this regimen. III. To assess overall and progression-free survival in this group of patients treated with this regimen. IV. To explore, in a preliminary manner, associations between gene expression signatures and response. OUTLINE: This is a multicenter study. Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (sorafenib tosylate)
Arm Type
Experimental
Arm Description
Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
sorafenib tosylate
Other Intervention Name(s)
BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Overall response rate (confirmed CR, R and PR)
Time Frame
Up to 3 years
Title
Incidence of qualitative and quantitative toxicities associated with this regimen
Time Frame
Up to 3 years
Title
Overall survival
Time Frame
Up to 3 years
Title
Progression-free survival
Time Frame
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have a confirmed diagnosis of previously treated, active multiple myeloma, with measurable disease present to evaluate response; all tests for establishing baseline disease status (serum protein electrophoresis, urine protein electrophoresis and bone marrow biopsy) must be performed within 28 days prior to registration and MUST be documented on the Baseline and Follow-up Tumor Assessment Form for Multiple Myeloma Patients must have relapsed or resistant disease, defined as relapsing after autologous stem cell transplantation or is either relapsing or is resistant after >= 1 line of prior therapy for myeloma; a minimum of 42 days must have elapsed since prior transplant Relapse: is defined as the occurrence of any of the following during or after previous treatment: A myeloma protein increase by more than 100% from the lowest previously recorded level A myeloma protein increase above the response criteria for PR Reappearance of any myeloma peak that had disappeared during the previous treatment Increase in the size and number of lytic bone lesions and/or focal lesions recognized in radiographic studies (x-ray, MRI, PET and/or CT scans) Resistant disease: is defined as disease not responding (i.e. not achieving CR, R, PR) to previous therapy Patients must be off myelosuppressive chemotherapy for >= 21 days (>= 6 weeks for nitrosoureas) and non-myelosuppressive chemotherapy and XRT for >= 14 days and recovered from all treatment associated toxicities prior to registration Patients must have a Zubrod Performance Status (PS) of 0-2 Patients must have received no prior treatment with BAY 43-9006 Patients must have currently have no significant neurotoxicity, defined as Grade >= 2 neurotoxicity per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Patients must have no evidence of POEMS (polyneuropathy, organomegaly, endocrinopathy, presence of M-protein, and skin changes) Syndrome There must be no active infection requiring antibiotics Bilirubin =< 1.5 times the institutional upper limit of normal (IULN) AST (SGOT or SGPT) =< 5 times the institutional upper limit of normal (IULN) Serum creatinine =< the institutional upper limit of normal (IULN) ANC > 750/ul Platelet count > 75,000/ul Patients must be able to take oral medication without crushing, dissolving or chewing tablets Patients must not be taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, and phenobarbital), rifampin, or St. John's Wort Patients must not have a significant history of cardiac disease, e.g., uncontrolled hypertension, unstable angina, congestive-heart failure, and myocardial infarction within the last six months, or cardiac ventricular arrhythmias requiring medication Patients must not have any evidence of bleeding diathesis, uncontrolled diabetes mellitus, or other serious or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol Patients must not be on therapeutic anticoagulation No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years Pregnant or nursing women may not participate in this trial because of increased risk of fetal harm including fetal death from the chemotherapeutic agents; women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method Institutions must have IRB approval of S0309 ("Myeloma Specimen Repository Protocol, Ancillary"); patients must be offered participation in S0309; with the patient's consent, bone marrow aspirates and serum specimens will be submitted for testing via S0309; patients must be registered separately to S0309 in order for institutions to receive credit for specimen submission to S0309; NOTE: immediately following S0434 registration, the CRA will need to have completed the S0309 Registration Form and eligibility worksheet in hand for use All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohamad Hussein
Organizational Affiliation
SWOG Cancer Research Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southwest Oncology Group
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78245
Country
United States

12. IPD Sharing Statement

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Sorafenib in Treating Patients With Relapsed or Refractory Multiple Myeloma

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