A Phase I/II Trial of Cabozantinib (XL184) in Patients With Relapsed or Refractory Myeloma

Memorial Sloan Kettering Cancer Center5 sites in 1 country11 target enrollmentMay 28, 2013

ConditionsRelapsed or Refractory Multiple Myeloma

InterventionsCabozantinib (XL184)

DrugsCabozantinib (XL184)

Overview

Phase: Phase 1
Intervention: Cabozantinib (XL184)
Conditions: Relapsed or Refractory Multiple Myeloma
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 11
Locations: 5
Primary Endpoint: Maximally Tolerated Dose
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is an open label phase I/II trial to investigate the safety and efficacy of Cabozantinib for patients with relapsed or refractory myeloma.

Registry

clinicaltrials.gov

Start Date

May 28, 2013

End Date

August 18, 2016

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•MSKCC confirmed diagnosis of multiple myeloma that has relapsed or is resistant after therapy with at least one immunomodulatory drug (i.e. lenalidomide, thalidomide) and at least one proteasome inhibitor.
•Age ≥ 18 years old.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0-
•The subject has organ and marrow function as follows:
•Absolute neutrophil count (ANC) ≥ 1500/mm3 (G-CSF is allowed).
•Platelets ≥ 50,000/mm3 or 30,000 (if marrow infiltrated with myeloma; no platelet transfusions are allowed in the 7 days prior to screening)
•Hemoglobin ≥ 8 g/dL (with transfusions). Bilirubin ≤ 1.5 × the upper limit of normal (ULN).
•Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 50 mL/min.
•Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN if no liver involvement, or ≤ 5 × ULN with liver involvement.
•Lipase \< 1.5 x the upper limit of normal.

Exclusion Criteria

•The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks, or nitrosoureas/ mitomycin C within 6 weeks before the first dose of study treatment.
•The subject has received radiation therapy within 14 days of the first dose of study treatment.
•The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment.
•The subject has not recovered from toxicity due to all prior therapies (i.e., return to pretherapy baseline or to Grade 0 or 1).
•The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test results at screening that are ≥1.3 ×ULN.
•The subject has uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled congestive heart failure, unstable angina pectoris within 6 months, stroke within 6 months, myocardial infarction within 6 months, or uncontrolled cardiac arrhythmias, uncontrolled hypertension.
•Corrected QTc of greater than 500msec.
•The subject is pregnant or breastfeeding.
•The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.
•The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (≤ 81 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted.

Arms & Interventions

Cabozantinib (XL184)

Eligible patients will receive cabozantinib as a tablet, orally daily. One cycle is defined as 28 days. Myeloma response will be assessed by IMWG criteria after each cycle. The DLT evaluation period will be six weeks. This trial will be a standard 3 by 3 dose escalation design, where three daily dose levels (20mg, 40mg, and 60mg) will be investigated.

Intervention: Cabozantinib (XL184)