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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01605227




Registration number
NCT01605227
Ethics application status
Date submitted
22/05/2012
Date registered
24/05/2012
Date last updated
14/03/2018

Titles & IDs
Public title
Study of Cabozantinib (XL184) Versus Prednisone in Men With Metastatic Castration-resistant Prostate Cancer Previously Treated With Docetaxel and Abiraterone or MDV3100
Scientific title
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
Secondary ID [1] 0 0
2012-001834-33
Secondary ID [2] 0 0
XL184-307
Universal Trial Number (UTN)
Trial acronym
COMET-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Castration Resistant Prostate Cancer 0 0
Pain 0 0
Prostatic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - cabozantinib
Treatment: Drugs - prednisone

Experimental: cabozantinib - Subjects randomized to the cabozantinib arm will also receive placebo-matched prednisone capsules.

Active comparator: prednisone - Subjects randomized to the prednisone arm will also receive placebo-matched cabozantinib.


Treatment: Drugs: cabozantinib
Tablets taken orally once-daily

Treatment: Drugs: prednisone
Taken twice a day orally. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
OS was measured from the time of randomization until 614 events, approximately 24 months after study start
Secondary outcome [1] 0 0
Bone Scan Response (BSR)
Timepoint [1] 0 0
BSR was measured at the end of Week 12 as determined by the IRF

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2015
Sample size
Target
Accrual to date
Final
1028
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
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- Albury
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- Concord
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- Darlinghurst
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- Kogarah
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- Port Macquarie
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- Randwick
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- Wahroonga
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- Westmead
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- South Brisbane
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- Southport
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- Woolloongabba
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- Adelaide
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- Kurralta Park
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- Hobart
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- Bentleigh East
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- Box Hill
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- Wodonga
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- Perth
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2640 - Albury
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2193 - Concord
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2010 - Darlinghurst
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2217 - Kogarah
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2444 - Port Macquarie
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2031 - Randwick
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2076 - Wahroonga
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2145 - Westmead
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4101 - South Brisbane
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4215 - Southport
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4102 - Woolloongabba
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5000 - Adelaide
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5037 - Kurralta Park
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7000 - Hobart
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3165 - Bentleigh East
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3128 - Box Hill
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3690 - Wodonga
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6000 - Perth
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Exelixis
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01605227
Trial related presentations / 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.
Smith M, De Bono J, Sternberg C, Le Moulec S, Oudard S, De Giorgi U, Krainer M, Bergman A, Hoelzer W, De Wit R, Bogemann M, Saad F, Cruciani G, Thiery-Vuillemin A, Feyerabend S, Miller K, Houede N, Hussain S, Lam E, Polikoff J, Stenzl A, Mainwaring P, Ramies D, Hessel C, Weitzman A, Fizazi K. Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1. J Clin Oncol. 2016 Sep 1;34(25):3005-13. doi: 10.1200/JCO.2015.65.5597. Epub 2016 Jul 11.
Public notes

Contacts
Principal investigator
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Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01605227