Clinical trial NCT01447914
Conditions: Refractory Multiple Myeloma
Keywords: c-Met Inhibitor ARQ-197 tivantinib multiple myeloma plasma cell proliferative disorder Hypercalcemia hematologic malignancy plasma cell dyscrasia cast nephropathy amyloidosis osteolysis Renal insufficiency Anemia Bone lytic lesions severe osteopenia pathologic fractures biopsy-proven plasmacytoma
Sponsor: National Cancer Institute (NCI)
Start date: 2011-11-01; Completion date: 2014-04-01
Enrollment: 16 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies the side effects and how well tivantinib works in treating patients with relapsed, or relapsed and refractory multiple myeloma. Tivantinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description:
PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.

OUTLINE:

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.

Arms: arm 1: 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.
Interventions: intervention 1: Tivantinib intervention 2: Diagnostic laboratory biomarker analysis intervention 3: Questionnaire administration intervention 4: Quality-of-life assessment
Intervention descriptions: intervention 1: 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. intervention 2: Correlative studies intervention 3: Ancillary studies intervention 4: Ancillary studies

Protocol documents: