A Study to Determine the Safety and Efficacy of Cabozantinib (XL184) in Patients with Metastatic Castration-resistant Prostate Cancer who have Received Prior Docetaxel and Prior Abiraterone or MDV3100
- Conditions
- Metastatic Castration-resistant Prostate Cancer (CRPC)MedDRA version: 17.0Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-001834-33-BE
- Lead Sponsor
- Exelixis, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 960
1.Documented histological or cytological diagnosis of prostate cancer.
2.Serum testosterone levels less than 50 ng/dL (< 1.75 nmol/L) within 28 days before randomization.
3.Evidence of bone metastasis related to prostate cancer on bone scans from a protocol-credentialed scanner using technetium-99m labeled methylene diphosphonate (Tc99-MDP) radiotracer within 28 days before randomization.
Note: Tc99-MDP is the preferred tracer. In situations where this tracer is unavailable, other tracers such as Tc99 dicarboxypropane diphosphonate (Tc99-DPD), Tc99 hydroxymethylene diphosphonate (Tc99-HDP), or Tc99-hidroximetilenodifosfonato (Tc99-HMDP) may be used. At the discretion of the Sponsor other Tc99 bone-seeking radiopharmaceuticals not designated above may be allowed.
4.The subject must have experienced disease
progression prior docetaxel (minimum cumulative dose of 225 mg/m2) and either abiraterone or MDV3100 treatment and have evidence of investigator-assessed prostate cancer progression on each agent independently.
For docetaxel: subjects must have progressed during or after docetaxel-containing therapy.
For abiraterone or MDV3100: subjects must have experienced disease progression during abiraterone or MDV3100 therapy.
Prostate cancer progression is defined as:
a.PSA progression according to PCWG2 (Prostate Cancer Working Group 2) criteria: PSA level of at least 2 ng/mL (2 µg/L) which has subsequently risen on at least 2 successive occasions, at least 2 weeks apart. If the second risen value is lower than the first risen value, then an additional test for rising PSA will be required to document progression. The value of the additional test must be higher than the first risen value (Scher et al. 2008).
or
b.Radiographic progression in soft tissue or bone lesions.
Note: There is no limit on other prior anti-cancer treatments, including prior cabazitaxel (except Exclusion Criterion #1).
5.Subjects without prior orchiectomy must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) therapy until permanent discontinuation of study treatment.
6.Subject must have recovered to baseline or CTCAE v.4.0 (Common Terminology Criteria for Adverse Events, version 4.0) = Grade 1 from toxicities related to any prior treatments, unless AE(s) are clinically non significant and/or stable on supportive therapy.
7.= 18 years old on the day of consent.
8.ECOG performance status: 0-2
9.Adequate organ and marrow function, defined as follows, based upon laboratory tests performed within 7 days before randomization:
a.Absolute neutrophil count (ANC) = 1500/mm3 (= 1.5 GI/L)
b.Platelets = 100,000/mm3 (= 100 GI/L)
c.Hemoglobin = 9 g/dL (= 90 g/L)
d.Total bilirubin = 1.5 x the upper limit of normal (for subjects with Gilbert’s disease, = 3 mg/dL or = 51.3 µmol/L)
e.Serum albumin = 3 g/dL (= 28 g/L)
f.Serum creatinine = 1.5 x the upper limit of normal or calculated creatinine clearance = 50 mL/min (= 0.84 mL/sec; by the Cockcroft –
Gault method) or GFR > 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 rat
1.The subject has 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 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 surg
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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. <br>;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 Outcome Measures
Name Time Method 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