NCT01866293 · REGISTRY CONDITION SEARCH

Cabozantinib (XL184) in Patients With Relapsed or Refractory Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2017-08-30

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Maximally Tolerated Dose

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outcome · POSTED

Overall Response Rate

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outcome · POSTED

Safety and Toxicity in This Patient Population

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outcome · POSTED

Time to Progression (TTP)

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outcome · POSTED

Duration of Response (DOR)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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 0-2. 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 * A documented serum follicle-stimulating hormone (FSH) level \> 35 mIU/mL (for women with irregular menstrual periods and on hormone replacement therapy) 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. * The subject has experienced any of the following within 6 months before the first dose of study treatment: 1. clinically-significant hematemesis or gastrointestinal bleeding 2. hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood 3. 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 * Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including: * Any of the following at the time of screening i) intra-abdominal tumor/metastases invading GI mucosa ii) active peptic ulcer disease, iii) inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis iv) malabsorption syndrome Any of the following within 6 months before the first dose of study treatment: i) history of abdominal fistula ii) gastrointestinal perforation iii) bowel obstruction or gastric outlet obstruction iv) intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more that 6 months ago. * History of major surgery as follows: 1. Major surgery within 3 months of the first dose of cabozantinib. Major surgery within 6 months of the first dose of cabozantinib if there are complications related to wound healing. 2. Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications (particularly when associated with delayed or incomplete healing) within 28 days. Note: Complete healing following abdominal surgery must be confirmed prior to initiating treatment with cabozantinib even if surgery occurred more that 28 days ago. * Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus. * Concurrent malignancy except for treated non-melanoma skin cancer and cervical carcinoma in situ. * The subject requires chronic concomitant treatment of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort).
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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 Names
Drug: Cabozantinib (XL184)
label
Cabozantinib (XL184)
type
EXPERIMENTAL

interventions

arm Group Labels
Cabozantinib (XL184)
name
Cabozantinib (XL184)
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 11
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
This trial will be a standard 3 by 3 dose escalation design, where three daily dose levels (20mg, 40mg, and 60mg) will be investigated.
measure
Maximally Tolerated Dose
time Frame
1 year

secondary Outcomes

description
IMWG Criteria for Response, Progression and Relapse in Multiple Myeloma Patients
measure
Overall Response Rate
time Frame
1 year
description
Safety assessments and toxicity grading will follow CTCAE Version 4 Grade
measure
Safety and Toxicity in This Patient Population
time Frame
1 year
measure
Time to Progression (TTP)
time Frame
1 year
measure
Duration of Response (DOR)
time Frame
1 year

Full study description

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.

Source references