Metastatic Castration-resistant Prostate Cancer (CRPC) MedDRA version: 17.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Cabozantinib 20mg
Product Code: XL184
Pharmaceutical Form: Tablet
INN or Proposed INN: Cabozantinib
CAS Number: 1140909-48-3
Current Sponsor code: XL184
Concentration unit: mg milligram(
Sponsors
Exelixis, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Documented histological or cytological diagnosis of prostate cancer. 2. Serum testosterone levels less than 50 ng/dL ( 30 mL/min (> 0.50 mL/sec). Note: For GFR estimation, the Cockcroft and Gault equation should be used [GFR = CrCl (mL/min) = (140 - age) x wt (kg)/(serum creatinine x 72)] g. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 x the upper limit of normal h. Lipase < 1.5 times the upper limit of normal i. Serum phosphorus = lower limit of normal j. Urine protein/creatinine ratio (UPCR) = 1 (= 113.17 mg/mmol creatinine) 10. The subject must be capable of understanding and complying with the protocol requirements and must have signed the informed consent document. 11. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including 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 treatment. Are the trial subje
Exclusion criteria
Exclusion criteria: 1. The subject received prior cabozantinib. 2. The subject has received docetaxel, abiraterone or MDV3100 within 2 weeks before randomization. 3. The subject has received any other type of anti-cancer agent (except agents to maintain castrate status) within 2 weeks before randomization. 4. The subject has received radiation therapy within 4 weeks (includes radiation targeting bone metastases) or radionuclide treatment within 6 weeks of randomization. Subject is excluded if there is any prior history of radiation therapy to the mediastinum (unless radiation targeted bone metastases). 5. The subject has known brain metastases or cranial epidural disease 6. The subject requires at the time of randomization therapeutic doses of anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or FXa inhibitors, antiplatelet agents (eg, clopidogrel), aspirin above low dose levels for cardioprotection per local applicable guidelines, or aspirin in combination with dipyridamole. Use of agents other than warfarin or warfarin-related agents is allowed if doses are in accordance with prescribing information for prophylaxis for thromboembolic events. Note: Therapeutic doses of heparin are allowed as clinically indicated for supportive treatment after randomization (see Section 7.2). 7. The subject requires chronic concomitant treatment of strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John’s Wort). 8. Uncontrolled and/or significant intercurrent illness including, but not limited to, the following conditions: a. Cardiovascular disorders such as symptomatic congestive heart failure (CHF), uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening), unstable angina pectoris, clinically-significant cardiac arrhythmias, history of stroke (including TIA, or other ischemic event) within 6 months before randomization, myocardial infarction within 6 months before randomization, history of thromboembolic event within 6 months before randomization b. Gastrointestinal disorders such as malabsorption syndrome or gastric outlet obstruction. c. Risks for GI perforation or fistula formation which include intra-abdominal tumor/metastases invading GI tract; active peptic ulcer disease, active inflammatory bowel disease, active ulcerative colitis, active diverticulitis, active cholecystitis or active symptomatic cholangitis or active appendicitis; history of abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess, or prior GI surgery (particularly when associated with delayed or incomplete healing) within 6 months before first dose of study treatment. Complete healing following abdominal surgery or resolution of intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib. d. Risk for non-GI fistula formation which includes previous surgical intervention (such as PEG tube placement) and evidence of intraluminal disease involving the trachea or esophagus. e. Other disorders such as active infection requiring systemic treatment; serious non-healing wound/ulcer/bone fracture; organ transplant; uncompensated hypothyroidism, uncontrolled diabetes mellitus f. History of surgery within 6 months before randomization: • With wound healing complications – major surgery within 6 months, minor surgery w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to evaluate the effect of cabozantinib compared to prednisone on overall survival in men with previously treated metastatic castration-resistant prostate cancer with bone-dominant disease who have experienced disease progression on docetaxel-containing chemotherapy and abiraterone or MDV3100. ;Secondary Objective: None.;Primary end point(s): Overall survival;Timepoint(s) of evaluation of this end point: Overall survival is defined as the time from the date of randomization to the date of death (due to any cause). Subjects not known to have expired at the time of analysis will generally be censored at the date last known alive. Detailed censoring rules for overall survival will be described in the SAP. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Bone scan response at the end of Week 12 by IRF. The stratified CMH test will be used as the primary analysis of this endpoint.;Timepoint(s) of evaluation of this end point: Week 12 | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Ireland, Italy, Netherlands, Puerto Rico, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactExelixis Medical Affairs
Exelixis, Inc.
Outcome results
None listed