Prostate Cancer
Conditions
Keywords
Rising PSA, androgen deprivation, bevacizumab (avastin), docetaxel, lupron, zoladex, bicalutamide
Brief summary
In this research study, we aim to evaluate the feasibility, toxicity and efficacy of early multimodality systemic therapy (a combination of docetaxe, bevacizumab, and androgen deprivation therapy(ADT) in men with biochemical recurrence (BCR) or who have a rising Prostate Specific Antigen (PSA) after treatment of their prostate cancer with surgery or radiation)
Detailed description
A single arm phase 2 study designed to evaluate the rate of patients free from Prostate Specific Antigen (PSA) progression (TTP) one year after completing ADT for men with BCR after definitive local therapy for prostate cancer. The null and alternative TTP rate were 41% and 60% respectively. A sample size of 42 would provide 80% power to detect the difference with a 2-sided type I error rate of 0.05.' The primary objective was to evaluate the proportion of patients free from PSA progression after completing one year of ADT The secondary objectives included 1. PSA response (\< 0.2 ng/mL and \< 0.01) at completion of docetaxel/bevacizumab, at completion of ADT and one year off ADT 2. Correlation of PSA response and TTP 3. Toxicity 4. Testosterone recovery at 6, 12 months off ADT Treatment schedule details are as follows: * Each treatment cycle lasts three weeks. During the first three months, participants will receive the Avastin and docetaxel on day 1 of each three-week cycle for a total of four doses of docetaxel/Avastin. Avastin and docetaxel are administered intravenously. The Avastin will continue to be given every three weeks after the docetaxel is completed for a total of 17 doses (one year) of Avastin therapy. * Participants will receive zoladex (or lupron) on day 1 of the first cycle and then every 3 months for a total of 18 months. Zoladex is administered subcutaneously and Lupron is administered intramuscularly. * Bicalutamide pills will be started at the completion of docetaxel chemotherapy (start of month 4) and will be taken once daily until hormone therapy is completed (total of 15 months). * During all treatment cycles, the participant will have a physical exam and will be asked questions about their general health and specific questions about any problems they might be experiencing. Blood work will be performed every three weeks for the first three months and then every three months while on hormone therapy and during follow-up. * After the final treatment participants will have a follow-up visit every three months for the first two years, every 4 months for the third year and every 6 months for years 4 and 5.
Interventions
DRUGDocetaxel
Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles
DRUGBevacizumab
Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles
DRUGADT
Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months)
DRUGBicalutamide
Starting on day 84 orally once daily until hormone therapy is completed
Sponsors
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Genentech, Inc.
Dana-Farber Cancer Institute
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
* 18 years of age or older * History of biopsy documented prostate cancer (any Gleason score) * Past treatment with prostatectomy with our without salvage prostate/pelvic radiation or primary radiation * If past prostatectomy, pathologic stage no greater than T1-3, N1, M0 * PSA recurrence with PSAdt 8 months or less. There is no minimum PSA for prostatectomy patients. For patients treated with primary radiation therapy PSA should be 2.0ng/ml or greater * No evidence of recurrent disease on exam, bone scan, CT/MRI abdomen/pelvis on CXR * Prior ADT allowed if less than 6 months and testosterone recovered to within 50 units of normal range * ECOG Performance status of 0-1 * Absolute neutrophil count of 1,500 mm3 or greater * Platelet Count 100,000 mm3 or greater * Total bilirubin within normal limits * HG 8gm/dl or greater * Testosterone within 50 units of normal range * No history of bleeding or thromboses within the last 12 months that required medical intervention
Exclusion criteria
* History of cancer within 5 years, other than prostate cancer and non-melanoma skin cancer * Medical condition requiring concomitant corticosteroids * Active infection * Prior chemotherapy * Neuropathy requiring medical therapy * Documented local recurrence or metastatic prostate cancer * Inability to comply with study and/or follow-up procedures * Life expectancy of less than 2 years * Current, recent (within 4 weeks of first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study * Inadequately controlled hypertension * Any prior history of hypertensive crisis or hypertensive encephalopathy * NYHA Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 12 months prior to study enrollment * History of stroke or transient ischemic attack at any time * Known CNS disease * Significant vascular disease * Symptomatic peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment * Serious, non-healing wound, ulcer, or bone fracture * Proteinuria at screening * Known hypersensitivity to any component of Avastin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prostate-Specific Antigen (PSA) Progression at 1 Year After Completing Androgen Deprivation Therapy (ADT) | participants were followed for the duration of the study, an average of 2 years | For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA \> 0.2 ng/mL. For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA \>2.0 ng/mL. Any new site of metastatic disease on imagining would be considered progression regardless of PSA value Clinical assessments (Vitals, Physical Exam, Performance Status, PSA and testosterone) were performed every 3 months starting at completion of hormone therapy until PSA progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With PSA Responses at One Year After the Completion of ADT | 1 year + 3 month off last ADT injection | The PSA response was defined using two cut-offs: PSA \<0.2 ng/mL or PSA \<0.01 ng/mL at the one year after completion of ADT. |
| Time to PSA Progression (TTP) | participants were followed for the duration of the study, an average of 2 years | For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA \> 0.2 ng/mL. For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA \> 2.0 ng/mL. Any new site of metastatic disease on imagining would be considered progression regardless of PSA value |
| Testosterone Recovery | 2 years | Testosterone recovery was defined as \>100 or within DFCI institute normal range (240-950) at one year after the completion of ADT |
| Toxicity | Assessed each cycle throughout treatment form time of first dose to 30 days post-treatment, up to 2 years | Treatment related adverse events were graded based on CTCAE v. 3.0. |
Countries
United States
Participant flow
Recruitment details
42 patients were enrolled between June 2, 2008 to December 14, 2010 at Dana Farber Cancer Institute and University of Michigan. One patient never started any study treatment, and was excluded from analysis.
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel, Bevacizumab, and Androgen Deprivation Therapy (ADT) Docetaxel:
Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles
Bevacizumab:
Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles
Androgen deprivation therapy (ADT) or Luteinizing hormone-releasing hormone agonist (LHRH):
Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months)
Bicalutamide:
Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months)
Docetaxel
Bevacizumab: intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles
ADT: Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months)
Bicalutamide: Starting on day 84 orally once daily until hormone therapy is completed | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | Docetaxel, Bevacizumab, and Androgen Deprivation Therapy (ADT) |
|---|---|
| Age, Continuous | 58 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| 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 | 21 / 41 |
Outcome results
Primary
Prostate-Specific Antigen (PSA) Progression at 1 Year After Completing Androgen Deprivation Therapy (ADT)
For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA \> 0.2 ng/mL. For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA \>2.0 ng/mL. Any new site of metastatic disease on imagining would be considered progression regardless of PSA value Clinical assessments (Vitals, Physical Exam, Performance Status, PSA and testosterone) were performed every 3 months starting at completion of hormone therapy until PSA progression.
Time frame: participants were followed for the duration of the study, an average of 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel, Bevacizumab, and ADT | Prostate-Specific Antigen (PSA) Progression at 1 Year After Completing Androgen Deprivation Therapy (ADT) | 98 percentage of participants with data |
Secondary
Proportion of Patients With PSA Responses at One Year After the Completion of ADT
The PSA response was defined using two cut-offs: PSA \<0.2 ng/mL or PSA \<0.01 ng/mL at the one year after completion of ADT.
Time frame: 1 year + 3 month off last ADT injection
Population: The analysis comprised of all patients received at least one treatment and had PSA data available\* for the assessment of PSA responses at one year after completing ADT~\*Note excluded 5 patients started treatments but had no PSA information at one year.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel, Bevacizumab, and ADT | Proportion of Patients With PSA Responses at One Year After the Completion of ADT | PSA <0.2 ng/mL | 44 percentage of participants with data |
| Docetaxel, Bevacizumab, and ADT | Proportion of Patients With PSA Responses at One Year After the Completion of ADT | PSA <=0.01 ng/mL | 25 percentage of participants with data |
Secondary
Testosterone Recovery
Testosterone recovery was defined as \>100 or within DFCI institute normal range (240-950) at one year after the completion of ADT
Time frame: 2 years
Population: All treated patients with assessable testosterone level data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel, Bevacizumab, and ADT | Testosterone Recovery | Testosterone >=100 ng/mL | 83 percentage of participants with data |
| Docetaxel, Bevacizumab, and ADT | Testosterone Recovery | Testosterone >=240 ng/mL | 35 percentage of participants with data |
Secondary
Time to PSA Progression (TTP)
For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA \> 0.2 ng/mL. For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA \> 2.0 ng/mL. Any new site of metastatic disease on imagining would be considered progression regardless of PSA value
Time frame: participants were followed for the duration of the study, an average of 2 years
Population: the analysis dataset is comprised of all treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel, Bevacizumab, and ADT | Time to PSA Progression (TTP) | 27.5 months |
Secondary
Toxicity
Treatment related adverse events were graded based on CTCAE v. 3.0.
Time frame: Assessed each cycle throughout treatment form time of first dose to 30 days post-treatment, up to 2 years
Population: All patients received at least one study therapies
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel, Bevacizumab, and ADT | Toxicity | Grade 3 treatment related AE | 16 participants |
| Docetaxel, Bevacizumab, and ADT | Toxicity | Grade 4 treatment related AEs | 5 participants |