Clinical trial NCT01347788: Cabozantinib (XL184) in Men With Castrate-Resistant Prostate Cancer
Official title: Dose-Finding Pilot Study of XL184 in Men With Castrate-Resistant Prostate Cancer and Bone Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Adenocarcinoma
Keywords: Prostate cancer
Castration Resistant
Bone Metastases
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-05-04
Enrollment: 34
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Cabozantinib (XL184) is a new drug that is being developed to treat cancer. Cabozantinib works by blocking the "angiogenesis," or the growth of new blood vessels, to the tumor. This is similar to how several other cancer drugs work but in addition Cabozantinib also blocks other pathways that may be responsible for allowing cancer cells to become resistant to these other "anti-angiogenic" treatments. So far cabozantinib has been investigated in treating brain cancer and a rare form of thyroid cancer. This study will explore lower doses of cabozantinib with the goal to find the most effective, safe, and tolerable dose without undesirable side effects.

Detailed description: Cabozantinib will be taken by mouth daily. The first five treatment cycles will be 21 days. All cycles after that will be 42 days long. Patients will keep a diary to record study drug dosing.

During the screening phase patients will receive a physical exam, blood and urine tests, a bone scan, a CT of the abdomen and pelvis, and an MRI scan of total body. On Day 1 of each cycle patients will receive a physical exam and blood and urine tests. Bone scan, CT and MRI scans will be performed at the start of cycles 3 and 5, and then repeated once every 12 weeks.

Patients will continue to receive study treatment as long as they are receiving benefit from the treatment, do not experience any severe or unmanageable side effects, and disease does not get any worse.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed prostate adenocarcinoma
* Bone metastases confirmed by bone scan
* Current androgen deprivation therapy
* Castration-resistant disease based on progression in bone and/or PSA progression
* Recovered from toxicities related to prior treatment, except alopecia, lymphopenia, other non-clinically significant adverse events
* Life expectancy of greater than 3 months
* Normal organ and marrow function
* Capable of understanding and complying with the protocol requirements
* Agree to use medically accepted methods of contraception
* Able to swallow capsules

Exclusion Criteria:

* More than two prior chemotherapy regimens for metastatic prostate cancer
* Known untreated, symptomatic or uncontrolled brain metastases
* Serious or unhealed wound
* Treatment with anticoagulants
* Previously identified allergy or hypersensitivity to components of the study treatment formulation
* History of a different malignancy unless disease-free for at least 5 years, or basal or squamous cell carcinoma of the skin
* Current antiretroviral therapy
* Uncontrolled hypertension
* Uncontrolled intercurrent illness

Primary outcomes:
measure: Partial Response in Bone Scan From Baseline to Week 6
timeFrame: Baseline and Week 6
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Matthew R Smith, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee RJ, Saylor PJ, Michaelson MD, Rothenberg SM, Smas ME, Miyamoto DT, Gurski CA, Xie W, Maheswaran S, Haber DA, Goldin JG, Smith MR. A dose-ranging study of cabozantinib in men with castration-resistant prostate cancer and bone metastases. Clin Cancer Res. 2013 Jun 1;19(11):3088-94. doi: 10.1158/1078-0432.CCR-13-0319. Epub 2013 Apr 3.