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Sorafenib and Bortezomib Treatment for Relapsed or Refractory Multiple Myeloma Patients
This study is currently recruiting participants.
Verified by Sarah Cannon Research Institute, June 2009
First Received: September 26, 2007   Last Updated: June 12, 2009   History of Changes
Sponsors and Collaborators: Sarah Cannon Research Institute
SCRI Oncology Research Consortium
Bayer
Information provided by: Sarah Cannon Research Institute
ClinicalTrials.gov Identifier: NCT00536575
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Sorafenib and Bortezomib
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase I/II Trial of Sorafenib and Weekly Bortezomib in the Treatment of Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Sarah Cannon Research Institute:

Primary Outcome Measures:
  • Objective response rate and progression-free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: November 2007
Estimated Study Completion Date: November 2009
Estimated Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Sorafenib and Bortezomib

    The brief Phase I portion will require cohorts of 3 patients per dose level as follows:

    Dose Level 1: The initial dose level of Sorafenib is 200 mg po bid continuous dosing of each 5 week course.

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

    Dose Level 2: Sorafenib 200 mg po bid continuous dosing of each 5 week course. Bortezomib 1.6 mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle.

    Dose Level 3: Sorafenib 400 mg po bid continuous dosing of each 5 week course. Bortezomib 1.6mg/m2 IV bolus on days 1, 8, 15, and 22 of each 5-week cycle.

    Patients in the Phase II portion will receive bortezomib and sorafenib at doses defined in the Phase I portion of the trial.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  • Patients must be accessible for treatment and follow-up procedures.
  • Patients must provide written informed consent prior to receiving protocol therapy.
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment.
  • Patients must be able to understand the nature of this study and give written informed consent.

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.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  • Age < 18 years.
  • Patients who have received any other experimental drug within 28 days of starting treatment.
  • Use of St. John's Wort or rifampin (rifampicin).
  • Any condition that impairs a patient's ability to swallow whole pills.
  • Patient with any non-healing wound or ulcer will not be eligible. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of sorafenib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00536575

Contacts
Contact: Ian W. Flinn, M.D. (615) 329-7274 iflinn@tnonc.com
Contact: Trials Info (615) 329-7274 trialsinfo@scresearch.net

Locations
United States, Maryland
Center for Cancer and Blood Disorders Recruiting
Bethesda, Maryland, United States, 20817
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37023
Sponsors and Collaborators
Sarah Cannon Research Institute
SCRI Oncology Research Consortium
Bayer
Investigators
Study Chair: Ian W. Flinn, M.D. SCRI Oncology Research Consortium
  More Information

Additional Information:
No publications provided

Responsible Party: SCRI Oncology Research Consortium ( Ian W. Flinn, M.D. )
Study ID Numbers: SCRI MM 14
Study First Received: September 26, 2007
Last Updated: June 12, 2009
ClinicalTrials.gov Identifier: NCT00536575     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by Sarah Cannon Research Institute:
Multiple Myeloma
Relapsed
Refractory
Sorafenib
Bortezomib

Study placed in the following topic categories:
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Bortezomib
Vascular Diseases
Paraproteinemias
Hemostatic Disorders
Protein Kinase Inhibitors
Protease Inhibitors
Multiple Myeloma
Hemorrhagic Disorders
Lymphoproliferative Disorders
Sorafenib
Neoplasms, Plasma Cell

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

ClinicalTrials.gov processed this record on September 11, 2009