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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Exelixis
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01428219
First received: August 30, 2011
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer Metastatic
Drug: Cabozantinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Cabozantinib (XL184) in Patients With Castrate-Resistant Prostate Cancer Metastatic to Bone

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Efficacy of cabozantinib in patients with castrate-resistant prostate cancer metastatic to bone. [ Time Frame: 12 weeks after participant initiates study ] [ Designated as safety issue: No ]
    Efficacy will be measured by the proportion of participants who remain progression-free at 12 weeks after initiation of the study.


Secondary Outcome Measures:
  • Toxicity. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • The effect of cabozantinib on bone lesions. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    • Changes in markers of bone metabolism in bone and serum with cabozantinib.
    • Changes in MET, AKT and VEGFR2 expression and phosphorylation status (activation) in osteoblasts/osteoclasts and prostate cancer cells from bone biopsy specimens with cabozantinib.
    • Changes in perfusion and diffusion MRI and CT images in bone lesions with cabozantinib and correlate those with response.

  • Progression-free survival. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Response proportion in both soft tissue and bone disease. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Duration of response. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • PSA response. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Time-to-progression. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 46
Study Start Date: February 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabozantinib (XL184)
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
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.
Other Name: XL184

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01428219

Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Exelixis
Investigators
Principal Investigator: David C. Smith, M.D. University of Michigan
  More Information

No publications provided

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01428219     History of Changes
Other Study ID Numbers: UMCC 2011.069, HUM00052320
Study First Received: August 30, 2011
Last Updated: October 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan Cancer Center:
Prostate
Cancer
Metastatic

Additional relevant MeSH terms:
Bone Marrow Diseases
Bone Neoplasms
Neoplasm Metastasis
Neoplasms
Prostatic Neoplasms
Bone Diseases
Genital Diseases, Male
Genital Neoplasms, Male
Hematologic Diseases
Musculoskeletal Diseases
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014