Clinical trial NCT01834651: A Phase II Study of Cabozantinib (XL184) Therapy in Castrate Resistant Prostate Cancer (CRPC) With Visceral Metastases
Official title: A Phase II Study of Cabozantinib (XL184) Therapy in Castrate Resistant Prostate Cancer (CRPC) With Visceral Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: liver metastasis
lung metastasis
metastatic castrate-resistant
prostate cancer
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
First posted: 2013-04-18
Enrollment: 17
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: This research study is being done to measure the clinical benefit associated with cabozantinib (XL184) in men who have prostate cancer that has spread to visceral organs (organs other than bone or lymph nodes) and no longer responds to initial hormonal (castration) therapy. This type of prostate cancer is called metastatic, castrate-resistant prostate cancer.

Detailed description: Cabozantinib (XL184), a multi-targeted tyrosine kinase inhibitor, has demonstrated a powerful clinical phenotype in men with metastatic castrate resistant prostate cancer (mCRPC) both before and after chemotherapy. This phenotype consists of rapid reduction in pain (when present) and improvement in bone scans that may or may not be accompanied by decrease in serum prostate specific antigen (PSA) concentrations. In previous studies of cabozantinib in advanced prostate cancer, patients with visceral disease have been excluded. Hence, this protocol creates a unique opportunity to define the activity of this disease in the population of men with visceral disease - a marker for poorer prognosis in mCRPC.

Primary Objectives:

- To assess the clinical benefit (complete response + partial response + stable disease) of cabozantinib in patients with mCRPC with visceral metastases.

Secondary Objectives:

* To assess the impact of cabozantinib on numbers live circulating tumor cells (CTCs) using NanoVelcro Chips
* To test the feasibility of measuring variation in gene expression in circulating tumor cells (CTCs) in response to therapy.
* To determine if there is an impact of cabozantinib on live circulating tumor cell (CTC) number and patterns of gene expression.
* To measure the impact of cabozantinib on serum HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor) levels in men with metastatic, castration-resistant prostate cancer (mCRPC).
* To assess the safety and tolerability of lower doses (i.e. doses below 100 mg daily) of cabozantinib in mCRPC with visceral involvement.
* To collect blood, urine, tissue, and plasma which may be used determine if there are germline genetic variations that correlate with toxicity.
* To pilot correlations between molecular content between circulating tumor cells (CTCs), large oncosomes, and tumor tissue.

Eligibility criteria: KEY INCLUSION CRITERIA

- mCRPC that includes visceral disease. Visceral metastatic disease is defined as solid organ infiltration that is not bone or lymph node metastases.

KEY EXCLUSION CRITERIA

* Recent history (\<6 months) of gastrointestinal hemorrhage requiring blood transfusion.
* Tumor involvement in the intestinal lining which the treating physician deems at risk for perforation with rapid tumor response.

Primary outcomes:
measure: Clinical Benefit Rate From Cabozantinib (XL184)
timeFrame: Baseline to 12 weeks after starting therapy
Secondary outcomes:
measure: Change in Number of Circulating Tumor Cells (CTC) in Response to Cabozantinib
timeFrame: Baseline and 12 weeks
measure: Number of Patients With NanoVelcro Appropriate for RNA in Circulating Tumor Cells
timeFrame: 12 weeks
measure: Change in Levels of Serum Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) Concentration
timeFrame: 12 weeks
measure: Number of Participants With Grade 3/4 Adverse Events Related to Cabozantinib as Assessed Using CTCAE (v.4)
timeFrame: Every 2 weeks for first 3 Cycles and every 4 weeks thereafter for an expected average of 28 weeks.
measure: Number of Patients With Evaluable Protein Content of Large Oncosomes From Baseline to First Documented Progression or Date of Death
timeFrame: From baseline until the date of first documented progression or date of death from any cause, whichever comes first, assessed for an expected average of 28 weeks.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute
name: Edwin Posadas, MD FACP
role: PRINCIPAL_INVESTIGATOR
References: