Adenocarcinoma of the Prostate, Prostate Cancer
Conditions
Keywords
prostate cancer, bevacizumab, docetaxel, radical prostatectomy
Brief summary
The main purpose of this trial is to collect information and to evaluate the effects, good or bad, the combination of docetaxel and bevacizumab has on patients with high risk prostate cancer that are undergoing radical prostatectomy.
Detailed description
* Patients who are eligible for this study will undergo an endorectal MRI scan test before beginning the research study. * After the MRI, the patient will begin the docetaxel plus bevacizumab part of the study. Each treatment cycle starts on the day you receive both drugs and lasts 21 days. Patients will undergo a total of 6 cycles-5 with docetaxel plus bevacizumab and one with docetaxel alone. * At the beginning of each cycle, the patient will come into the clinic for a visit that will last about 3 hours. The following will happen at these visits: physical examination including vital signs and rectal exam; questions about the patients health and the medications they are taking; blood tests (both routine and research blood tests); urine tests; bevacizumab infusion; docetaxel infusion. * The patients first dose of bevacizumab will be given on Day 1 of the first cycle over 90 minutes. If the patient tolerates the 90-minute infusion well, later doses may be given over a shorter period of time. * The day before and the morning of the beginning of each cycle, the patient will be given a steroid called dexamethasone in pill form to help decrease the side effects of the treatment. * The above tests and procedures will be repeated every 21 days a total of five times. For the sixth time, the patient will have all the same tests and procedures except they will not receive bevacizumab. * After the six cycles, the patient will undergo another endorectal MRI. * One to two months after finishing the sixth cycle, the patient will undergo a radical prostatectomy to remove their prostate. * Two to three months after the surgery the patient will return to the clinic to have the following tests and procedures: questions about the patient's health; routine blood tests and research blood tests.
Interventions
DRUGBevacizumab
Bevacizumab (marketed as Avastin, Genentech) is an antibody to all isoforms of vascular endothelial growth factor and is the first putative anti-angiogenic agent approved by the Food and Drug Administration (FDA) for the treatment of cancer.All subjects will be treated with intravenous docetaxel and bevacizumab for 5 cycles, followed by docetaxel alone for Cycle 6. Bevacizumab will be given first, at a starting dose of 15 mg/kg. Bevacizumab will be given once every 21 days in the infusion center.
DRUGDocetaxel
Docetaxel will be given intravenously once every 21 days in the infusion center. The starting dose is 70mg/square meter.
Sponsors
Beth Israel Deaconess Medical Center
Duke University
Genentech, Inc.
Sanofi
Mary-Ellen Taplin, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological documentation of adenocarcinoma of the prostate, with available biopsy pathology. Material from this biopsy must be available for central review at DF/HCC by the beginning of the second cycle of therapy. * Potential candidate for radical prostatectomy * Must meet one or more of the below characteristics: Gleason score of 8, 9 or 10; serum PSA of greater than or equal to 20 ng/mL; clinical T stage of T3; PSA velocity of greater than or equal to 2ng/mL/year in the year prior to diagnosis; Gleason score of 7 and erMRI T3 disease; Greater than or equal to 50% of the total number of biopsy cores positive for prostate cancer and either PSA \> 10ng/mL or Gleason score of 7 or clinical T stage of T2a, T2b or T2c. * Greater than six weeks since any major surgery * Serum testosterone \> 100ng/dL * ECOG Performance Status of 0 or 1 * ANC \> 1,500/ul * Platelets \> 100,000/ul * Total bilirubin, alkaline phosphatase, AST and ALT within normal limits * Creatinine \< 2.0 x upper limit of normal
Exclusion criteria
* History of prior radiation, surgery or hormonal therapy treatment for prostate cancer * Clinical evidence of metastatic prostate cancer * Ongoing oral steroid use * Pre-existing neuropathy of grade 2 or greater * Severe claustrophobia, inability to lie still in a magnet for 60 minutes, a pacemaker, or any other condition that would preclude proximity to a strong magnet. * History of the following conditions: unstable angina; symptomatic, clinically significant peripheral vascular disease; NY Heart Association Grade 2 or greater heart failure; uncontrolled hypertension; myocardial infarction or stroke \< 12 months prior to enrollment; uncontrolled hypertension; active, uncontrolled infection; history of DVT, PE or known coagulopathy or bleeding diathesis; ongoing us of anticoagulant therapy; history of abdominal fistulas, GI perforation, or intra-abdominal abscess within 6 months prior to study entry; non-healing ulcer or fracture; history of another malignancy diagnosed within the last five years; spot urine protein: creatinine ratio \> 1.0 at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endorectal MRI Response After Completion of 6 Cycles of Neoadjuvant Therapy | after 6 months of neoadjuvant chemotherapy. | A response was defined as a decrease in tumor size of \>50% for the largest lesion in the prostate by endorectal MRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response After Completing 6 Cycles of Neoadjuvant Chemotherapy. | after 6 months of ajuvant chemotherapy. | The rate of PSA decline by 50% compared to baseline PSA. |
Countries
United States
Participant flow
Recruitment details
42 subjects were consented, screened, registered and enrolled between 7/27/06 and 3/24/09 in the relevant clinics at Duke University (5 subjects) and DF/HCC (37 subjects).
Pre-assignment details
No subjects were found to be ineligible after signing the informed consent form and registering with the QACT.
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy docetaxel and bevacizumab prior to prostatectomy
Docetaxel : Docetaxel will be given intravenously once every 21 days in the infusion center. The starting dose is 70mg/square meter.
Bevacizumab : Bevacizumab (marketed as Avastin, Genentech) is an antibody to all isoforms of vascular endothelial growth factor and is the first putative anti-angiogenic agent approved by the Food and Drug Administration (FDA) for the treatment of cancer.All subjects will be treated with intravenous docetaxel and bevacizumab for 5 cycles, followed by docetaxel alone for Cycle 6. Bevacizumab will be given first, at a starting dose of 15 mg/kg. Bevacizumab will be given once every 21 days in the infusion center. | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Neoadjuvant Chemotherapy | Adverse Event | 2 |
| Neoadjuvant Chemotherapy | Disease progression | 1 |
| Neoadjuvant Chemotherapy | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Chemotherapy |
|---|---|
| Age, Continuous Between 18 and 65 years | 55 year |
| Region of Enrollment United States | 41 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 41 / 41 |
| serious Total, serious adverse events | 11 / 41 |
Outcome results
Primary
Endorectal MRI Response After Completion of 6 Cycles of Neoadjuvant Therapy
A response was defined as a decrease in tumor size of \>50% for the largest lesion in the prostate by endorectal MRI.
Time frame: after 6 months of neoadjuvant chemotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy | Endorectal MRI Response After Completion of 6 Cycles of Neoadjuvant Therapy | 0.29 proportion of participants |
Secondary
PSA Response After Completing 6 Cycles of Neoadjuvant Chemotherapy.
The rate of PSA decline by 50% compared to baseline PSA.
Time frame: after 6 months of ajuvant chemotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy | PSA Response After Completing 6 Cycles of Neoadjuvant Chemotherapy. | 0.22 proportion of participants |