Prostate Adenocarcinoma
Conditions
Keywords
Prostate cancer, Castration Resistant, Bone Metastases
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.
Interventions
DRUGcabozantinib
Cabozantinib PO QD
Sponsors
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Partial Response in Bone Scan From Baseline to Week 6 | Baseline and Week 6 | Bone scans will be centrally reviewed and categorized based on comparison of week 6 and baseline imaging. Partial response is defined as 30% or greater decrease in bone scan lesion area from baseline to week 6. An adaptive response design to determine the lowest effective cabozantinib dose among three dose levels (dose level +1, dose level 0 and dose level +1) will be employed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cabozantinib Final results have been published Clin Cancer Res. 2013 Jun 1;19(11):3088-94. doi: 10.1158/1078-0432.CCR-13-0319. Epub 2013 Apr 3.
A dose-ranging study of cabozantinib in men with castration-resistant prostate cancer and bone metastases.
Lee RJ, Saylor PJ, Michaelson MD, Rothenberg SM, Smas ME, Miyamoto DT, Gurski CA, Xie W, Maheswaran S, Haber DA, Goldin JG, Smith MR.
Author information Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA. rjlee@partners.org | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Cabozantinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 66 years |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 11 | 0 / 10 | 2 / 13 |
| serious Total, serious adverse events | 1 / 11 | 0 / 10 | 1 / 13 |
Outcome results
Primary
Partial Response in Bone Scan From Baseline to Week 6
Bone scans will be centrally reviewed and categorized based on comparison of week 6 and baseline imaging. Partial response is defined as 30% or greater decrease in bone scan lesion area from baseline to week 6. An adaptive response design to determine the lowest effective cabozantinib dose among three dose levels (dose level +1, dose level 0 and dose level +1) will be employed.
Time frame: Baseline and Week 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Partial Response in Bone Scan From Baseline to Week 6 | 9 participants |
| Cohort 2 | Partial Response in Bone Scan From Baseline to Week 6 | 1 participants |
| Expansion Cohort | Partial Response in Bone Scan From Baseline to Week 6 | 6 participants |