Trial of Cabozantinib (XL184) in Castrate-Resistant Prostate Cancer Metastatic to Bone

NCT01428219 | Terminated Phase 2 Results DMC

• 2 other identifiers: UMCC 2011.069HUM00052320
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer Metastatic

Keywords

Prostate; Cancer; Metastatic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Remain Progression-free at 12 Weeks

  Efficacy will be measured by the proportion of participants who remain progression-free at 12 weeks after initiation of the study. RECIST 1.1 will be used to measure progression. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or the appearance of one or more new lesions. Kaplan-Meier methods will be used to report progression-free survival.

  12 weeks after participant initiates study

Secondary Outcomes (7)

• Incidence of Adverse Events (AEs) Related to Treatment

  18 months

• Mean Fold Change in Bone Metabolism Biomarker Expression With Cabozantinib

  18 months

• Progression-free Survival

  12 weeks

• Response Proportion in Both Soft Tissue and Bone Disease.

  18 months

• Duration of Response.

  18 months

Study Arms (1)

Cabozantinib (XL184)

EXPERIMENTAL

Cabozantinib is available in capsule form. The dose is 60 mg daily by mouth. Subjects with disease progression at 6 weeks who do not have significant toxicities may remain on therapy for an additional six weeks until a progression is confirmed. Further study drug administration beyond 12 weeks will be at the discretion of the investigator provided that the subject does not have disease progression, does not have unacceptable side effects, does not withdraw from study, or does not have a medical condition or illness that renders the subject unacceptable to receive further study drug.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Cabozantinib is available in capsule form. The dose is 60 mg daily by mouth. Subjects with disease progression at 6 weeks who do not have significant toxicities may remain on therapy for an additional six weeks until a progression is confirmed. Further study drug administration beyond 12 weeks will be at the discretion of the investigator provided that the subject does not have disease progression, does not have unacceptable side effects, does not withdraw from study, or does not have a medical condition or illness that renders the subject unacceptable to receive further study drug.

Also known as: XL184

Cabozantinib (XL184)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Exelixis: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. David C. Smith, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

dcsmith@umich.edu

734-764-3066

Study Officials

• David C. Smith, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2011
• First Posted: September 2, 2011
• Study Start: February 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: September 1, 2015
• Last Updated: December 12, 2017
• Results First Posted: May 2, 2016

Record last verified: 2017-11

Locations

US (1)