The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01522443




Registration number
NCT01522443
Ethics application status
Date submitted
13/01/2012
Date registered
31/01/2012
Date last updated
23/05/2018

Titles & IDs
Public title
Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer
Scientific title
A Phase 3, Randomized, Double-blind, Controlled Trial of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer
Secondary ID [1] 0 0
XL184-306
Universal Trial Number (UTN)
Trial acronym
COMET-2
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 - mitoxantrone
Treatment: Drugs - prednisone

Experimental: Cabozantinib - Subjects randomized to the cabozantinib arm will also receive placebo mitoxantrone injections (color-matched with methylene blue) and placebo prednisone capsules.
There will be a maximum of 10 infusions for mitoxantrone placebo.

Active Comparator: Mitoxantrone/prednisone - Subjects randomized to the mitoxantrone + prednisone arm will also receive placebo cabozantinib tablets.
There will be a maximum of 10 infusions for mitoxantrone.


Treatment: Drugs: cabozantinib
Tablets taken orally once daily.

Treatment: Drugs: mitoxantrone
Given by IV once every 3 weeks.

Treatment: Drugs: prednisone
Taken twice a day orally by mouth. 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
Pain Response at Week 6 Confirmed at Week 12, Week 12 Reported - The pre-specified primary analysis of Pain Response at Week 6 confirmed at Week 12 was defined as = 30% from baseline in the average daily worst pain intensity score during a 7-day reporting period, with neither a concomitant increase in average daily use of any opioid narcotic type, nor addition of any new opioid narcotic type, relative to baseline. Pain Progression at a given time point is defined as = 30% increase compared with baseline in the average daily worst pain intensity score during a 7-day reporting period or either an increase in the average daily use of any type of opioid narcotic or addition of a new opioid narcotic type compared with baseline.
Timepoint [1] 0 0
Pain response was measured at Week 6 and Week 12 by self-reports of subjects
Secondary outcome [1] 0 0
Bone Scan Response (BSR) - BSR is defined as >=30% in the bone scan lesion area (BSLA) compared with baseline. Bones scans were evaluated by an independent radiology facility (IRF) for response.
Timepoint [1] 0 0
BSR was measured at the end of Week 12 as determined by the IRF
Secondary outcome [2] 0 0
Overall Survival (OS) - OS was defined as the time from randomization to the date of death (due to any cause). Participants that had not died were censored at last known date alive. The analyses for OS occurred after 78/196 deaths (40% of the total required for the pre-specified primary analysis of OS). The data cut-off date was 06 October 2014. Median OS was calculated using Kaplan-Meier estimates.
Timepoint [2] 0 0
OS was measured at the time of randomization until 78 deaths

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.

- Documented pain from bone metastases that requires opioid narcotic intervention.

- Adopted a narcotic regimen that consists of one sustained release opioid agent taken
daily for chronic pain and one immediate release opioid agent for breakthrough pain.

- Received prior docetaxel and either abiraterone or MDV3100 treatment and has evidence
of investigator assessed 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.

- A left-ventricular ejection fraction (LVEF) of >/= 50% assessed by echocardiogram or
MUGA (multigated acquisition scan).

- Capable of understanding and complying with the protocol requirements (including
having the ability to access an interactive voice recognition system and self-report
pain and narcotic use) 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 3
months after the last dose of study treatment.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment with cabozantinib or mitoxantrone.

- 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 therapy in the last 4 weeks (includes radiation targeting bone metastases),
radionuclide treatment in the last 6 weeks, or radiation therapy to the thoracic
cavity (unless radiation targets bone metastases) in the past 3 months.

- Treatment with serotonergic psychiatric medication(s) in the last 2 weeks (5 weeks for
fluoxetine).

- Known brain metastases or uncontrolled epidural disease.

- Requires concomitant treatment, in therapeutic doses, with anticoagulants such as
warfarin or warfarin-related agents, heparin, thrombin or FXa (coagulation factor X)
inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (above low dose
levels for cardioprotection per local applicable guidelines), low-dose warfarin (= 1
mg/day), and prophylactic low molecular weight heparin are permitted.

- 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 of > 0.5 teaspoon of red blood, 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.

- Corrected QT interval (QTc) > 500 ms in the last 4 weeks.

- Unable to swallow capsules or tablets or tolerate infusions.

- Previously-identified allergy or hypersensitivity to components of the study treatment
formulations investigator or designee.

- History of another malignancy (except non-melanoma skin cancer, adequately treated
stage I colon cancer, superficial transitional carcinoma of the bladder) in the past 2
years.

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
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
- Concord
Recruitment hospital [2] 0 0
- Darlinghurst
Recruitment hospital [3] 0 0
- Kogarah
Recruitment hospital [4] 0 0
- Port Macquarie
Recruitment hospital [5] 0 0
- Randwick
Recruitment hospital [6] 0 0
- Wahroonga
Recruitment hospital [7] 0 0
- Milton
Recruitment hospital [8] 0 0
- South Brisbane
Recruitment hospital [9] 0 0
- Woolloongabba
Recruitment hospital [10] 0 0
- Box Hill
Recruitment hospital [11] 0 0
- Wodonga
Recruitment hospital [12] 0 0
- Subiaco
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [5] 0 0
2031 - Randwick
Recruitment postcode(s) [6] 0 0
2076 - Wahroonga
Recruitment postcode(s) [7] 0 0
4064 - Milton
Recruitment postcode(s) [8] 0 0
4101 - South Brisbane
Recruitment postcode(s) [9] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [10] 0 0
3128 - Box Hill
Recruitment postcode(s) [11] 0 0
3690 - Wodonga
Recruitment postcode(s) [12] 0 0
- Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Maryland
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Minnesota
Country [16] 0 0
United States of America
State/province [16] 0 0
Mississippi
Country [17] 0 0
United States of America
State/province [17] 0 0
Missouri
Country [18] 0 0
United States of America
State/province [18] 0 0
Nebraska
Country [19] 0 0
United States of America
State/province [19] 0 0
Nevada
Country [20] 0 0
United States of America
State/province [20] 0 0
New Jersey
Country [21] 0 0
United States of America
State/province [21] 0 0
New York
Country [22] 0 0
United States of America
State/province [22] 0 0
North Carolina
Country [23] 0 0
United States of America
State/province [23] 0 0
Ohio
Country [24] 0 0
United States of America
State/province [24] 0 0
Oklahoma
Country [25] 0 0
United States of America
State/province [25] 0 0
Pennsylvania
Country [26] 0 0
United States of America
State/province [26] 0 0
South Dakota
Country [27] 0 0
United States of America
State/province [27] 0 0
Tennessee
Country [28] 0 0
United States of America
State/province [28] 0 0
Texas
Country [29] 0 0
United States of America
State/province [29] 0 0
Utah
Country [30] 0 0
United States of America
State/province [30] 0 0
Virginia
Country [31] 0 0
United States of America
State/province [31] 0 0
Washington
Country [32] 0 0
United States of America
State/province [32] 0 0
Wisconsin
Country [33] 0 0
Canada
State/province [33] 0 0
British Columbia
Country [34] 0 0
Canada
State/province [34] 0 0
Ontario
Country [35] 0 0
Ireland
State/province [35] 0 0
Dublin
Country [36] 0 0
United Kingdom
State/province [36] 0 0
England
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Scotland
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Belfast

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Exelixis
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Bone metastases and associated pain are a major cause of morbidity and mortality in
castration-resistant prostate cancer (CRPC). Most approved therapies have shown some ability
to reduce soft tissue lesions but none meaningfully impacts bone metastases (as demonstrated
by lack of resolution of lesions on bone scan with these agents) or the pain associated with
these metastases.

This study will evaluate the effect of cabozantinib versus mitoxantrone plus prednisone on
pain response and bone scan response in men with CRPC.
Trial website
https://clinicaltrials.gov/show/NCT01522443
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01522443