Sorafenib and Bortezomib Treatment for Relapsed or Refractory Multiple Myeloma Patients

January 23, 2013 updated by: SCRI Development Innovations, LLC

Phase I/II Trial of Sorafenib and Weekly Bortezomib in the Treatment of Patients With Relapsed or Refractory Multiple Myeloma

This is a single-arm Phase I/II study of sorafenib and bortezomib with dose optimization in initial patients. The initial patients on the dose-finding portion of this study will be enrolled through a single institution. Following establishment of the Phase II dose the study will open enrollment throughout the Sarah Cannon Research Institute (SCRI) Oncology Research Consortium.

The purpose of this study is to develop the combination of bortezomib (which is proven to be clinically active in patients with multiple myeloma) with sorafenib (a potent inhibitor of angiogenesis). This regimen will be developed in a schedule that is convenient for patients, and that is as minimally toxic to patients as possible.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary Objective:

To evaluate the efficacy of sorafenib with weekly bortezomib, as measured by objective response rate and progression-free survival in patients with relapsed/refractory multiple myeloma.

Secondary Objective:

To evaluate the feasibility and toxicity of sorafenib with weekly bortezomib in the treatment of patients with relapsed/refractory multiple myeloma.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Center for Cancer and Blood Disorders
    • Tennessee
      • Nashville, Tennessee, United States, 37023
        • Tennessee Oncology, PLLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Eligible participants must have been previously diagnosed using standard criteria and have received no more than 2 prior regimens for the treatment of multiple myeloma.
  • Participant must be defined as Relapsed or Refractory Disease by one of the following criteria prior to enrollment: Relapsed Disease after high-dose therapy (autologous stem cell transplantation) as part of the first-line line treatment program. These patients may have received a maximum of 1 previous regimen, Refractory Disease or Relapsed Disease after > 1 prior therapy for multiple myeloma. Prior bortezomib treatment permitted if the patient achieved a documented response.
  • ECOG performance status 0, 1, or 2.
  • WBC >= 3000; ANC >= 1000; platelets >= 50,000 (Patients with platelets >= 30,000 are eligible if thrombocytopenia is felt to be due to extensive bone marrow involvement with myeloma).
  • Serum creatinine < 2.0 mg/dL for a calculated or measured creatinine clearance > 30 mL/minute
  • Total bilirubin < 1.5 x ULN
  • ALT and AST < 2.5 x the ULN ( < 5 x ULN for patients with liver involvement)
  • INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
  • Patients must have measurable or evaluable disease. In patients with disease limited to bone and bone marrow, serial paraprotein measurements are acceptable for evaluable disease.

Exclusion Criteria:

  • Patients with > grade 1 peripheral neuropathy.
  • Thrombolic or embolic events such as a cerebrovascular accident, including transient ischemic attacks, within the past 6 months.
  • Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
  • Known brain metastasis. Patients with neurological symptoms must undergo CT scan/MRI of the brain to exclude brain metastasis.
  • Patients with other medical conditions that would potentially interfere with their participation in this trial.
  • Patients with other active malignancies, or history of treatment for other invasive cancers, within 3 years of study entry.
  • Patients with previous evidence of hypersensitivity to sorafenib, bortezomib, boron, or mannitol.
  • Women who are pregnant or lactating are ineligible. All patients of childbearing potential are required to use adequate methods of contraception while receiving study treatment, and for at least 2 weeks after the last dose of sorafenib. Men should continue to use contraception until at least 3 months after their last dose of sorafenib.
  • Evidence of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome.
  • Cardiac disease: Congestive heart failure > class II NYHA (see Appendix D.) Patients must not have unstable angina (anginal symptoms at rest), new onset angina (began within the last 3 months), or myocardial infarction within the past 6 months.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  • Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
  • Active clinically serious infection > CTCAE Grade 2.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
The trial was designed as a single-arm Phase I/II study of sorafenib and bortezomib with dose optimization in initial patients. Phase I consisted of cohorts of 3 patients at each of three dose levels. Patients received bortezomib (Dose Level 1 - 1.3 mg/m2; Dose Level 2 - 1.6 mg/m2) by IV bolus on days 1, 8, 15, and 22 of each 5-week cycle with continuous oral dosing of sorafenib at 200 mg twice daily. Dose level 3 was planned as bortezomib 1.6 mg/m2 IV bolus on days 1, 8, 15, and 22 with sorafenib 400 mg by mouth twice daily throughout each 5-week cycle.
Drug: Bortezomib

Dose Level 1: Bortezomib 1.3mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle.

Dose Level 2: Bortezomib 1.6 mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle.

Dose Level 3: Bortezomib 1.6mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle.

Other Names:
  • Velcade
Drug: Sorafenib

Dose Levels 1 and 2: 200 mg by mouth twice daily

Dose Level 3: 400 mg by mouth twice daily

Other Names:
  • Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
Time Frame: 24 months
The percentage of patients who experience an objective benefit from treatment, determined by the treating physician after reviewing key laboratory values from blood and urine.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SCRI Development Innovations, LLC

Collaborators

Bayer

Investigators

  • Study Chair: Ian W. Flinn, M.D., SCRI Development Innovations, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

February 1, 2010

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

September 26, 2007

First Submitted That Met QC Criteria

September 27, 2007

First Posted (Estimate)

September 28, 2007

Study Record Updates

Last Update Posted (Estimate)

February 27, 2013

Last Update Submitted That Met QC Criteria

January 23, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCRI MM 14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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