Sorafenib and Bortezomib in Treating Patients With Advanced Cancer

NCT00303797 | Completed Phase 1

• 3 other identifiers: NCI-2009-00124MC0511U01CA069912
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (4)

• MTD as assessed by the number of patients with dose-limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

  DLTs include: Hematologic: Grade 4 ANC for ≥5 days, Grade 4 anemia of any duration, or PLT \<25,000 of any duration; Renal: Serum creatinine ≥2 times baseline or \> 2x upper limit of normal if baseline levels normal; All other non-hematologic toxicities ≥grade 3 as per CTCAE v3.0 except fatigue; Any toxicities that caused dose delay of \> 2 weeks of the intended next dose. MTD is the dose level below the lowest dose that induces DLT in at least one-third of patients (2 of 6 patients).

  Observed for at least 3 weeks at a given dose level combination

• Toxicity as assessed by CTCAE v3.0

  Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via Common Toxicity Criteria standard grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  Observed for at least 3 weeks at a given dose level combination

• Antitumor activity as assessed by tumor measurement or evaluation of indicator lesion by computed tomography (CT) or magnetic resonance imaging (MRI)

  Baseline, prior to each course (every 3 weeks) during dose escalation, every 6 weeks for solid tumors, and confirmatory scans at least 4 weeks following initial documentation of objective response

• Effects of sorafenib on the disposition of bortezomib

  Up to 20 patients with hematologic malignancies will be treated at the MTD to evaluate markers of drug activity and pharmacokinetics of this combination.

  From cohort II registration prior to each course

Secondary Outcomes (4)

• Tumor response as assessed by CT or MRI using modified Response Evaluation Criteria in Solid Tumors (RECIST)

  Baseline, every 3 weeks during dose escalation, every 6 weeks for solid tumors, and confirmatory scans at least 4 weeks following initial documentation of objective response

• Best overall response as assessed using modified RECIST

  Baseline until disease progression/recurrence

• Duration of overall response

  From the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date recurrent or progressive disease is documented

• Duration of stable disease

  From the start of the treatment until the criteria for progression are met

Study Arms (1)

Treatment (bortezomib, sorafenib tosylate)

EXPERIMENTAL

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.

Drug: 17-N-allylamino-17-demethoxygeldanamycin/bortezomib; Drug: sorafenib tosylate

Interventions

17-N-allylamino-17-demethoxygeldanamycin/bortezomib DRUG

Treatment (bortezomib, sorafenib tosylate)

sorafenib tosylate DRUG

Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN

Treatment (bortezomib, sorafenib tosylate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 23887852 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma

Interventions

tanespimycin; Bortezomib; Sorafenib

Condition Hierarchy (Ancestors)

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

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

Study Officials

• Shaji Kumar

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 15, 2006
• First Posted: March 17, 2006
• Study Start: December 1, 2005
• Primary Completion: May 1, 2010
• Last Updated: March 19, 2013

Record last verified: 2013-03

Locations

US (1)