Magnetic Resonance Imaging in Measuring the Effect of Cabozantinib in Patients With Castrate Resistant Prostate Cancer

A Phase II Study of MRI Based Functional Imaging for the Evaluation of Bone Metastasis in Men With Castrate Resistant Prostate Cancer Receiving XL184

This study is being done to help researchers understand more about prostate cancer that has spread to the bones by using the newest magnetic resonance imaging (MRI) techniques and to better understand the effect of an experimental drug called XL184 (or cabozantinib) on bone disease. The other purposes of the study are to better understand the effect of XL184 on prostate cancer progression, bone pain, and on any cancer cells that patients may have circulating within the blood (called circulating tumor cells)

Study Overview

• Status: Completed
• Conditions: Recurrent Prostate Cancer; Bone Metastases; Stage IV Prostate Cancer; Castrate-resistant Prostate Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: cabozantinib; Procedure: magnetic resonance imaging

Detailed Description

PRIMARY OBJECTIVES:

I. To determine effect of XL184 on the functional MRI metrics Ktrans and apparent diffusion coefficient (ADC) within castrate resistant prostate cancer bone metastases.

SECONDARY OBJECTIVES:

I. To quantify progression free survival in men with castrate resistant prostate cancer (CRPC) treated with XL184 according to Prostate Cancer Working Group criteria.

II. To correlate and changes in MRI based functional metrics with bone scan, prostate specific antigen (PSA), Response Evaluation Criteria in Solid Tumors (RECIST) response criteria, circulating tumor cells (CTC) number and with changes in pain.

III. To explore c-MET, phospho-c-MET staining on circulating tumor cells as a predictive biomarker for response and duration of response to XL-184.

OUTLINE:

Patients receive cabozantinib orally (PO) once daily (QD). Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histologically or cytologically confirmed prostate cancer with progressive disease
• Evidence of castration resistance defined as disease progression despite a testosterone level < 50ng/dL (or surgical castration)
• Evidence of metastatic disease to the bones within the lumbar spine, sacrum, or pelvic bones that is identifiable on screening pelvic MRI
• If patient has had prior pelvis radiation therapy (RT), then bone metastases must be out of radiated port (e.g. lumbar or sacral spine)
• Any prior therapy for castrate disease acceptable other than prior XL184 with a minimum washout of 28 days for any other anticancer therapy

• Patients with castrate resistant disease post antiandrogen therapy/withdrawal must meet at least one of the following criteria:

  • Have not received docetaxel chemotherapy
  • Have received docetaxel chemotherapy but received less then 225mg/m2 cumulative dose
  • Have documented liver metastases
  • Have no pain or pain that does not require a long acting (SR) narcotic
  • Have received mitoxantrone chemotherapy in the past for CRPC

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
• Patients who are receiving any other investigational agents
• Prior treatment with other vascular endothelial growth factor (VEGF) or c-MET targeted therapies
• History of hematemesis or hemoptysis
• The subject has uncontrolled or significant intercurrent illness
• The patient requires concomitant treatment, in therapeutic doses, with anticoagulants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (enzyme inhibitor therapy); Patients receive cabozantinib PO QD. Treatment continues in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: cabozantinib; Given PO; Other Names: XL184; Procedure: magnetic resonance imaging; Undergo MRI; Other Names: MRI; NMRI; nuclear magnetic resonance imaging; NMR imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Functional MRI Metrics Ktrans Between 2 Weeks and Baseline	Ktrans is a measurement calculating the volume transfer constant of the contrast reagent and essentially is a measurement of vascular perfusion. To determine the effect of XL184 on the functional MRI metrics Ktrans, Ktrans parameters were measured at baseline, two week time-point, 12 weeks, and 24 weeks for disease monitoring. Change between baseline and 2 weeks reported.	baseline, 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of Progression Free Survival (PFS) With Ktrans and ADC	Time to progression or progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. The approximate survival after standard therapies in this setting is bleak and in the order of months. Too few events for a meaningful statistical analysis; no significant results were obtained in Cox regression analyses. Therefore, we calculated the median PFS time and its 95% confidence interval.	From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year
Changes in Bone Scan Response	Bone Scan Response at weeks 2, 12, and 24 were collected. Change between baseline and 2 weeks are reported Bone Scan Response were measured as increase, decrease, or stable of bone lesions and scored as 1, -1, or 0, respectively, where higher values represent a worse outcome.	baseline, 2 weeks
Correlation of Percent Change in the Functional MRI Metrics to RECIST Tumor Measurements	The protocol proposed to collect RECIST tumor measurements at weeks 0, 12, and 24. However, the data were not collected	baseline, 12 weeks, and 24 weeks
Change of PSA Between 12 Weeks and Baseline	PSA at weeks 0, 12, and 24 were collected. Change between baseline and 12 weeks are reported	baseline, 12 weeks
Correlation of Percent Change in the Functional MRI Metrics With CTC	The protocol proposed to collect CTC measurements at weeks 0, 12, and 24. However, the data were not collected	baseline, 12 weeks, and 24 weeks
Change in Pain Scale Between 12 Weeks and Baseline	Pain scores are measured at baseline and weeks 12, and 24. Change between baseline and 12 weeks are reported . In the pain score ranged from 0 to 10. 10 denotes most pain.	baseline,12 weeks

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: NorthShore University HealthSystem

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: May 14, 2012
• First Submitted That Met QC Criteria: May 15, 2012
• First Posted (Estimate): May 16, 2012

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: cabozantinib; CRPC; XL184; castrate resistant prostate cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Prostatic Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: 12-1031; NCI-2012-00677 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No