Sorafenib and Bortezomib Treatment for Relapsed or Refractory Multiple Myeloma Patients

NCT00536575 | Completed Phase 1 Results

• 1 other identifier: SCRI MM 14
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Relapsed; Refractory; Sorafenib; Bortezomib

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment

  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

Study Arms (1)

Intervention

EXPERIMENTAL

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; Drug: Sorafenib

Interventions

Bortezomib DRUG

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.

Also known as: Velcade

Intervention

Sorafenib DRUG

Dose Levels 1 and 2: 200 mg by mouth twice daily Dose Level 3: 400 mg by mouth twice daily

Also known as: Nexavar

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Bayer: collaborator

Study Sites (2)

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Related Links

• Sarah Cannon Research Institute

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Bortezomib; Sorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Limitations and Caveats

The 15% response rate was substantially lower than the designed rate of 60% for this trial. Coupled with the influx of new compounds for the treatment of multiple myeloma it was decided that this study should be closed early.

Results Point of Contact

• Title: John Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• Ian W. Flinn, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2007
• First Posted: September 28, 2007
• Study Start: November 1, 2007
• Primary Completion: February 1, 2010
• Study Completion: August 1, 2010
• Last Updated: February 27, 2013
• Results First Posted: February 27, 2013

Record last verified: 2013-01

Locations

US (2)