Sorafenib and Bortezomib in Treating Patients With Advanced Cancer

NCT ID: NCT00303797

Last Updated: 2013-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31

Brief Summary

This phase I trial is studying the side effects and best dose of sorafenib and bortezomib in treating patients with advanced cancer. Sorafenib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of cancer cells by blocking blood flow to the cancer

Detailed Description

OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of sorafenib and bortezomib in patients with advanced malignancies.

II. To describe the toxicities associated with the combination of sorafenib and bortezomib.

III. To evaluate the therapeutic antitumor activity of the combination of sorafenib and bortezomib.

IV. To evaluate the effects of sorafenib on the disposition of bortezomib.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 groups according to disease type.

GROUP I (solid tumors-dose-escalation group): Patients receive oral sorafenib twice daily on days 1-21 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of sorafenib and bortezomib until the 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.

GROUP II (multiple myeloma or chronic lymphocytic leukemia-maximum tolerated dose [MTD] group): Patients receive oral sorafenib at the MTD twice daily on days 3-21 of course 1 and on days 1-21 of each subsequent course. Patients also receive bortezomib IV over 3-5 seconds at the MTD on days 1, 4, 8, and 11.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 3 months.

Conditions

Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Multiple Myeloma; Stage IV Chronic Lymphocytic Leukemia; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (bortezomib, sorafenib tosylate)

GROUP I (solid tumors-dose-escalation group): Patients receive oral sorafenib twice daily on days 1-21 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of sorafenib and bortezomib until the 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.

GROUP II (multiple myeloma or chronic lymphocytic leukemia-maximum tolerated dose [MTD] group): Patients receive oral sorafenib at the MTD twice daily on days 3-21 of course 1 and on days 1-21 of each subsequent course. Patients also receive bortezomib IV over 3-5 seconds at the MTD on days 1, 4, 8, and 11.

Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

17-N-allylamino-17-demethoxygeldanamycin/bortezomib

Intervention Type: DRUG

sorafenib tosylate

Intervention Type: DRUG

Interventions

17-N-allylamino-17-demethoxygeldanamycin/bortezomib

Intervention Type: DRUG

sorafenib tosylate

Intervention Type: DRUG

Other Intervention Names

BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN

Eligibility Criteria

Inclusion Criteria

• Diagnosis of 1 of the following:

• Cytologically or histologically proven unresectable solid tumor for which no curative treatment options exist (group I - dose-escalation phase)
• Multiple myeloma or chronic lymphocytic leukemia requiring treatment (group II - maximum tolerated dose phase)

• Failed ≥ 1 prior regimen
• Non-secretory myeloma allowed
• No known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
• Tumor amenable to serial sampling (group II)
• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100,000/mm^3 (75,000/mm^3 for patients with multiple myeloma [group II])
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 3 times ULN (5 times ULN if liver involvement)
• Creatinine ≤ 1.5 times ULN (2.5 times ULN for patients with multiple myeloma [group II])
• Life expectancy ≥ 12 weeks
• No uncontrolled infection
• No New York Heart Association class III or IV heart disease
• No uncontrolled hypertension, labile hypertension, or history of poor compliance with antihypertensive medication
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No sensory peripheral neuropathy of any etiology > grade 1 or neuropathic pain of any etiology
• No active HIV infection requiring therapy
• No inability to swallow that would preclude use of oral medications
• No evidence of bleeding diathesis
• Medically capable and willing to provide biologic specimens as required (mandatory for patients in group II)
• Priorbortezomib allowed
• More than 3 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas) and recovered
• More than 4 weeks since prior immunotherapy or biologic therapy
• More than 2 weeks since prior steroid therapy (group II only)
• No prior anti-vascular endothelial growth factor therapy
• More than 4 weeks since prior full-field radiotherapy (2 weeks for limited-field radiotherapy)
• No prior radiation to > 25% of bone marrow
• More than 4 weeks since major surgery (e.g., laparotomy) (2 weeks for minor surgery)

• Insertion of a vascular access device is not considered major or minor surgery
• No concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary other therapy considered investigational
• No concurrent prophylactic colony-stimulating factors
• No concurrent therapeutic anticoagulation

• Concurrent 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, and phenobarbital), rifampin, or Hypericum perforatum (St. John's Wort)
• No concurrent participation in any other study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy), either for symptom control, or therapeutic intent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shaji Kumar

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

Kumar SK, Jett J, Marks R, Richardson R, Quevedo F, Moynihan T, Croghan G, Markovic SN, Bible KC, Qin R, Tan A, Molina J, Kaufmann SH, Erlichman C, Adjei AA. Phase 1 study of sorafenib in combination with bortezomib in patients with advanced malignancies. Invest New Drugs. 2013 Oct;31(5):1201-6. doi: 10.1007/s10637-013-0004-2. Epub 2013 Jul 26.

Reference Type: DERIVED

PMID: 23887852 (View on PubMed)

Other Identifiers

MC0511

Identifier Type: -

Identifier Source: secondary_id

U01CA069912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00124

Identifier Type: -

Identifier Source: org_study_id