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

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ClinicalTrials.gov Identifier: NCT01605227
Recruitment Status : Completed
First Posted : May 24, 2012
Results First Posted : March 14, 2018
Last Update Posted : March 14, 2018
Sponsor:
Information provided by (Responsible Party):
Exelixis

Study Description
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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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Castration Resistant Prostate Cancer Pain Prostatic Neoplasms Drug: cabozantinib Drug: prednisone Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1028 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Study Start Date : July 2012
Actual Primary Completion Date : September 2014
Actual Study Completion Date : March 2015

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Arms and Interventions
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Arm Intervention/treatment
Experimental: cabozantinib
Subjects randomized to the cabozantinib arm will also receive placebo-matched prednisone capsules.
 Drug: cabozantinib
Tablets taken orally once-daily
Other Name: XL184
Active Comparator: prednisone
Subjects randomized to the prednisone arm will also receive placebo-matched cabozantinib.
 Drug: prednisone
Taken twice a day orally. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01605227


  Show 264 Study Locations
Sponsors and Collaborators
Exelixis
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT01605227     History of Changes
Other Study ID Numbers: XL184-307
2012-001834-33 ( EudraCT Number )
First Posted: May 24, 2012    Key Record Dates
Results First Posted: March 14, 2018
Last Update Posted: March 14, 2018
Last Verified: February 2018

Keywords provided by Exelixis:
prostate cancer
castration resistant prostate cancer
bone pain
CRPC

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Prednisone
Antineoplastic Agents
 Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal