Study of Cabozantinib (XL184) Versus Prednisone in Men With Metastatic Castration-resistant Prostate Cancer Previously Treated With Docetaxel and Abiraterone or MDV3100 (COMET-1)

Tracking Information
First Submitted Date ICMJE	May 22, 2012
First Posted Date ICMJE	May 24, 2012
Results First Submitted Date	May 23, 2017
Results First Posted Date	March 14, 2018
Last Update Posted Date	March 14, 2018
Study Start Date ICMJE	July 2012
Actual Primary Completion Date	September 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 14, 2018)	Overall Survival (OS) [ Time Frame: OS was measured from the time of randomization until 614 events, approximately 24 months after study start ]; The primary analysis of OS is defined as the time from randomization to death due to any cause. Participants that had not died or were permanently lost to follow-up were censored at the last known date alive. Median OS was calculated using Kaplan-Meier estimates. Analysis for OS was performed after 614 events had occurred.
Original Primary Outcome Measures ICMJE; (submitted: May 23, 2012)	Overall survival [ Time Frame: Through 21 months after study start ]
Change History	Complete list of historical versions of study NCT01605227 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 14, 2018)	Bone Scan Response (BSR) [ Time Frame: BSR was measured at the end of Week 12 as determined by the IRF ]; BSR is defined as >=30% reduction in the bone scan lesion area (BSLA) compared with baseline. Confirmation of bone scan was not required for response or progression. Bone scans were evaluated by an independent radiology facility (IRF) for response.
Original Secondary Outcome Measures ICMJE; (submitted: May 23, 2012)	Bone scan response [ Time Frame: End of Week 12 ]; Bone scans will be evaluated by an independent radiology facility for response
Current Other Outcome Measures ICMJE; (submitted: February 14, 2018)	Progression-free Survival (PFS) [ Time Frame: Duration of PFS was defined as time from the date of randomization to earlier of date of radiographic progression (bone/andor soft tissue) according to the investigator's assessment or death, assessed for up to approximately 24 months ]; The exploratory analysis of PFS is the time from randomization to date of first documented radiographic progression (bone and/or soft tissue) according to the investigator's assessment or death. PFS was defined per mRECIST 1.1 and included evaluation of measurable, nonmeasurable, target and nontarget lesions. A Kaplan-Meier analysis was performed to estimate the median duration.
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Study of Cabozantinib (XL184) Versus Prednisone in Men With Metastatic Castration-resistant Prostate Cancer Previously Treated With Docetaxel and Abiraterone or MDV3100
Official Title ICMJE	A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) Versus Prednisone in Metastatic Castration-resistant Prostate Cancer Patients Who Have Received Prior Docetaxel and Prior Abiraterone or MDV3100
Brief Summary	This study will 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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Prostate Cancer; Castration Resistant Prostate Cancer; Pain; Prostatic Neoplasms
Intervention ICMJE	Drug: cabozantinib Tablets taken orally once-daily Other Name: XL184; Drug: prednisone Taken twice a day orally. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.
Study Arms	Experimental: cabozantinib Subjects randomized to the cabozantinib arm will also receive placebo-matched prednisone capsules. Intervention: Drug: cabozantinib; Active Comparator: prednisone Subjects randomized to the prednisone arm will also receive placebo-matched cabozantinib. Intervention: Drug: prednisone
Publications *	Heller G, McCormack R, Kheoh T, Molina A, Smith MR, Dreicer R, Saad F, de Wit R, Aftab DT, Hirmand M, Limon A, Fizazi K, Fleisher M, de Bono JS, Scher HI. Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials. J Clin Oncol. 2018 Feb 20;36(6):572-580. doi: 10.1200/JCO.2017.75.2998. Epub 2017 Dec 22.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 23, 2015)	1028
Original Estimated Enrollment ICMJE; (submitted: May 23, 2012)	960
Actual Study Completion Date	March 2015
Actual Primary Completion Date	September 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Histological or cytological diagnosis of castration resistant prostate cancer (serum testosterone less than 50 ng/dL).; Evidence of bone metastasis related to prostate cancer on bone scans.; Received prior docetaxel (minimum cumulative dose of 225 mg/m2) and either abiraterone or MDV3100 treatment and has evidence of prostate cancer progression on each agent independently.; Maintenance of LHRH agonist or antagonist unless treated with orchiectomy.; Recovered from toxicities related to any prior treatments, unless the toxicities are clinically non significant or easily manageable.; Adequate organ and marrow function.; Capable of understanding and complying with the protocol requirements and signed the informed consent form.; Sexually active fertile patients 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. Exclusion Criteria: Prior treatment with cabozantinib.; Treatment with docetaxel, abiraterone, or MDV3100 in the last 2 weeks; or with any other type of cytotoxic or investigational anticancer agent in the last 2 weeks.; Radiation within 4 weeks (excluded if to mediastinum) or radionuclide treatment within 6 weeks of randomization.; Known brain metastases or cranial epidural disease.; Requires concomitant treatment, in therapeutic doses, with anticoagulants.; Requires chronic concomitant treatment of strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's Wort).; Uncontrolled, significant intercurrent illness including, but not limited to, cardiovascular disorders, gastrointestinal disorders, active infections, non-healing wounds, recent surgery.; Clinically significant hematemesis or hemoptysis, or other signs indicative of pulmonary hemorrhage in the last 3 months, or history of other significant bleeding in the past 6 months.; Cavitating pulmonary lesion(s) or a lesion invading or encasing a major blood vessel.; QTcF > 500 ms within 7 days of randomization.; Unable to swallow capsules or tablets.; Previously-identified allergy or hypersensitivity to components of the study treatment formulations.; Another diagnosis of malignancy requiring systemic treatment within 2 years of randomization.
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia, Austria, Belgium, Canada, France, Germany, Ireland, Italy, Netherlands, Puerto Rico, Spain, Sweden, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01605227
Other Study ID Numbers ICMJE	XL184-307; 2012-001834-33 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Exelixis
Study Sponsor ICMJE	Exelixis
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Exelixis
Verification Date	February 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP