Cabozantinib (XL184) in Patients With Relapsed or Refractory Myeloma

NCT01866293 | Completed Phase 1 Results

• 1 other identifier: 12-240
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

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.

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

Cabozantinib (XL184); 12-240

Outcome Measures

Primary Outcomes (1)

• Maximally Tolerated Dose

  This trial will be a standard 3 by 3 dose escalation design, where three daily dose levels (20mg, 40mg, and 60mg) will be investigated.

  1 year

Secondary Outcomes (4)

• Overall Response Rate

  1 year

• Safety and Toxicity in This Patient Population

  1 year

• Time to Progression (TTP)

  1 year

• Duration of Response (DOR)

  1 year

Study Arms (1)

Cabozantinib (XL184)

EXPERIMENTAL

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.

Drug: Cabozantinib (XL184)

Interventions

Cabozantinib (XL184) DRUG

Cabozantinib (XL184)

Eligibility Criteria

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

You may qualify if:

• 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 0-2.
• 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.
• Patient must be able/willing to undergo bone marrow aspirate and biopsy.
• Subjects with brain metastasis or CNS disease are considered eligible if the subject has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for 2 or more weeks.
• Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g. male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control.
• Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is defined as:
• Amenorrhea ≥ 12 consecutive months without another cause OR

You may not qualify if:

• 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.
• The subject has experienced any of the following within 6 months before the first dose of study treatment:
• clinically-significant hematemesis or gastrointestinal bleeding
• hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood
• any other signs indicative of pulmonary hemorrhage The subject has radiographic evidence of cavitating pulmonary lesion(s)
• The subject has tumor in contact with, invading or encasing major blood vessels

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Exelixis: collaborator

Study Sites (5)

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center

Sleepy Hollow, New York, 10591, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Sergio Giralt, MD
• Organization: Memorial Sloan Kettering Cancer Center

GiraltS@mskcc.org

212-639-6009

Study Officials

• Sergio Giralt, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 28, 2013
• First Posted: May 31, 2013
• Study Start: May 28, 2013
• Primary Completion: August 18, 2016
• Study Completion: August 18, 2016
• Last Updated: August 30, 2017
• Results First Posted: August 30, 2017

Record last verified: 2017-02

Locations

US (5)