Tivantinib in Treating Patients With Relapsed, or Relapsed and Refractory Multiple Myeloma
|Refractory Multiple Myeloma||Drug: Tivantinib Other: Diagnostic laboratory biomarker analysis Other: Questionnaire administration Procedure: Quality-of-life assessment||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase II Study of the c-Met Inhibitor ARQ 197 in Patients With Relapsed, or Relapsed and Refractory Multiple Myeloma|
- Overall Response Rate (ORR) [ Time Frame: Up to 30 days ]ORR using International Myeloma Working Group Response Criteria, achieve at least a partial response (PR) or better: Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR): CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90%; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24 hour; Stable Disease (SD): Not CR, VGPR, PR or progressive disease; Progressive Disease (PD):>25% from lowest value Serum and/or Urine M-component, new lesions or soft tissue plasmacytomas, or hypercalcemia.
- Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 [ Time Frame: Up to 30 days ]Toxicities with a grade 3 nonhematologic or grade 4 hematologic toxicities according to CTCAE, version 4. Grade 3 and estimated with a 95% credible interval. Summary statistics will be provided for continuous variables.
- Progression-free Survival (PFS) [ Time Frame: From start of the treatment to disease progression or death (regardless of cause of death), whichever comes first, assessed up to 30 days ]Kaplan and Meier product limit methods will be used to estimate the median PFS with 95% confidence intervals. Furthermore, the univariate and multivariate Cox proportional hazards regression model will be used to identify prognostic factors for PFS.
- Duration of Response [ Time Frame: From first observation of partial response to the time of disease progression, assessed up to 30 days ]Kaplan and Meier product limit methods will be used to estimate the DOR with 95% confidence intervals.
- Time to Next Treatment (TTNT) [ Time Frame: From registration on trial to next treatment or death due to any cause, whichever comes first, assessed up to 30 days ]Kaplan and Meier product limit methods will be used to estimate the TTNT with 95% confidence intervals.
|Study Start Date:||November 2011|
|Study Completion Date:||April 2014|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: ARQ 197 Treatment (Tivantinib)
Oral Tivantinib 360 mg twice daily continuously for each day (days 1-28) of every 4-week treatment cycle (taken as three tablets of 120 mg each). Courses continue every 28 days in the absence of disease progression or unacceptable toxicity.
Given at a dose of 360 mg oral (PO) twice daily continuously for each day of every 4-week treatment cycle, which will be taken as three tablets of 120 mg each.
Other Names:Other: Diagnostic laboratory biomarker analysis
Correlative studiesOther: Questionnaire administration
Ancillary studiesProcedure: Quality-of-life assessment
Other Name: quality of life assessment
I. To determine the overall response rate of patients with relapsed, or relapsed and refractory multiple myeloma treated with the c-Met inhibitor ARQ 197 (tivantinib) as a single agent.
II. To define the toxicities of single agent ARQ 197 in a population of patients with relapsed, or relapsed and refractory multiple myeloma.
I. To obtain preliminary evidence of the durability of responses to single agent ARQ 197, including the progression free survival (PFS), the duration of response (DOR), and the time to next treatment (TTNT).
II. To correlate the activation status of the hepatocyte growth factor (HGF)/c-Met pathway in primary myeloma cells at baseline, as defined by gene expression profiling and reverse phase protein array data, with the above measures of efficacy of ARQ 197.
III. To correlate serum and marrow HGF, HGF activator (HGFA), and soluble c-Met (sc-Met) levels with the activation status of the HGF/c-Met pathway in primary myeloma cells at baseline, and with the above measures of efficacy of ARQ 197.
I. To evaluate the symptom burden of relapsed, or relapsed and refractory multiple myeloma patients undergoing therapy with single agent ARQ 197 using the M. D. Anderson Symptom Inventory (MDASI) and its multiple myeloma module (MDASI-MM) II. To evaluate the impact of therapy with single agent ARQ 197 for relapsed, or relapsed and refractory multiple myeloma on patient reported outcomes using the European Organization for Research on the Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (QLQ-C30), and the myeloma-specific module QLQ-MY20.
III. To evaluate the impact of therapy with single agent ARQ 197 for relapsed, or relapsed and refractory multiple myeloma on the ability to collect stem cells in any patients who go on to undergo subsequent stem cell mobilization.
Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28. Courses continue every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood, urine, and bone marrow collection for gene expression profile, proteomic profiling, and other correlative studies. Patients may complete the MDASI and its MDASI-MM, the EORTC QLQ-C30, and the myeloma-specific module QLQMY20 questionnaires at baseline and periodically during study.
After completion of study treatment, patients are followed up for 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01447914
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Robert Orlowski||M.D. Anderson Cancer Center|