Clinical trial NCT01428219: Trial of Cabozantinib (XL184) in Castrate-Resistant Prostate Cancer Metastatic to Bone
Official title: A Phase II Trial of Cabozantinib (XL184) in Patients With Castrate-Resistant Prostate Cancer Metastatic to Bone
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer Metastatic
Keywords: Prostate
Cancer
Metastatic
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: Exelixis
First posted: 2011-09-02
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to look at the effects of cabozantinib on castrate-resistant prostate cancer metastatic (cancer that has spread to other parts of the body) to the bone and to learn about any side effects caused by taking cabozantinib.

Detailed description: A significant proportion of patients with prostate cancer develop metastatic disease, which most commonly affects the skeleton. Bone metastases are the cause of significant morbidity and mortality in these patients, and require long-term management. Study participants in this research study will have a diagnosis of castration-resistant prostate cancer metastatic to bone.

Cabozantinib is not approved by the United States Food and Drug Administration (FDA) to treat people for castration-resistant prostate cancer metastatic to bone or for any other type of cancer. Giving cabozantinib to human cancer patients is experimental. Cabozantinib is currently being given to patients on other studies. Cabozantinib is known to have anti-tumor effects and to reduce bone metastases based on early clinical studies in prostate cancer and other cancers. The drug is known to have side effects. The most common side effects were fatigue, diarrhea, anorexia, rash, and palmar-plantar erythrodysesthesia (PPE) syndrome. To date, it is not known if cabozantinib is safe and/or effective.

Eligibility criteria: Inclusion Criteria:

* Pathologically and radiologically confirmed castrate-resistant prostate cancer metastatic to bone
* Bone metastases which are accessible for biopsy under CT guidance.
* Willingness to undergo sequential biopsy of bone lesions.
* No prior standard chemotherapy for metastatic disease (neoadjuvant, adjuvant and hormonal treatments are excluded).
* Participant must have discontinued antiandrogen therapy at least 4 weeks (for flutamide and megestrol acetate) or 6 weeks (for bicalutamide or nilutamide) prior to the first dose of XL184. Participants currently on LHRH or GnRH agonists can be maintained on these agents.
* Greater than or equal to 18 years old on day of consent
* Participants must be able to care for themselves
* Adequate organ and bone marrow function
* Participants must be capable of understanding and complying with the protocol requirements and has signed the informed consent document.
* Men capable of sexual activity will be required to agree to use a condom during sexual contact with women having the potential to bear children during their participation in the study and for six months after participation.

Exclusion Criteria:

* Prior therapy with cabozantinib
* Any other type of investigational agent within 28 days before the first dose of study treatment or 5 half-lives of the compound or active metabolite, whichever is longer
* No radiation therapy within 14 days of study treatment. No radionuclide treatment within two months.
* No known brain metastases.
* Test results that measure how quickly blood clots need to be adequate for the study
* Participants who require concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (≤ 81 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted.
* Participants must not have uncontrolled significant illness including but not limited to: ongoing or active infection requiring systemic treatment, symptomatic congestive heart failure, uncontrolled hypertension , history of hypertensive emergency (e.g.encephalopathy) or hypertensive urgency within 6 months of study treatment, clinically significant wounds including osteonecrosis, history of organ transplant, unstable angina pectoris, stroke within 3 months of study drug, heart attack within 3 months of study drug, development of clots within blood vessels within 6 months of study drug, bleeding from distended veins within 3 months of study drug, any other severe or life threatening hemorrhage/bleeding, major surgery within 4 weeks of study treatment, clinically significant cardiac arrhythmias, history of bowel obstruction within 6 months of study drug or unresolved malabsorption syndrome, untreated bone fracture including tumor-related pathologic fracture, anticipated need for major surgery during the period of the study.
* Corrected QT interval, as measured by an ECG, must be within acceptable protocol limits within 28 days of entering the study
* Unable to swallow capsules
* Unable to undergo MRI
* History of another malignant disease within two years with the exception of superficial skin or bladder cancer which has been completely resected or carcinoma in situ without evidence of invasion.

Primary outcomes:
measure: Percentage of Participants Who Remain Progression-free at 12 Weeks
timeFrame: 12 weeks after participant initiates study
Secondary outcomes:
measure: Incidence of Adverse Events (AEs) Related to Treatment
timeFrame: 18 months
measure: Mean Fold Change in Bone Metabolism Biomarker Expression With Cabozantinib
timeFrame: 18 months
measure: Progression-free Survival
timeFrame: 12 weeks
measure: Response Proportion in Both Soft Tissue and Bone Disease.
timeFrame: 18 months
measure: Duration of Response.
timeFrame: 18 months
measure: The Number of Patients That Are Progression Free by PSA
timeFrame: 12 weeks
measure: Median Time to PSA Progression
timeFrame: 18 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: David C. Smith, M.D.
role: PRINCIPAL_INVESTIGATOR
References: