Prostate Cancer
Conditions
Keywords
Androgen deprivation therapy, ADT, bevacizumab
Brief summary
The purpose of this research study is to assess the efficacy of antiangiogenic therapy (bevacizumab) and androgen deprivation versus androgen deprivation alone at the time of minimal systemic disease (based on rising PSA without metastases).
Detailed description
* Participants will be randomized into one of two study groups. The first group will receive Androgen Deprivation Therapy (ADT) plus bevacizumab. The second group will receive ADT alone. * For the Androgen Deprivation therapy either (treating physician discretion)leuprolide or goserelin acetate (given as injections) every 3 months for a total of 6 months. Bicalutamide will also be taken orally daily for a total of 6 months. * Bevacizumab will be given intravenously every three weeks for a total of 8 infusions over 6 months. * Participants will be evaluated every 7-9 weeks with vitals, physical exam, PS, laboratories including PSA and testosterone.
Interventions
DRUGAndrogen Deprivation Therapy
leuprolide: 22.5mg given IM every 3 months for a total of 6 months or, goserelin acetate: 10.8mg given SC every 3 months for a total of 6 months
DRUGbicalutamide
50mg orally daily for 6 months
DRUGbevacizumab
15mg/ks given IV every three weeks for a total of 8 infusions over 6 months
Sponsors
Genentech, Inc.
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Rutgers Cancer Institute of New Jersey
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of biopsy documented prostate cancer (any Gleason score) * Past treatment with prostatectomy with or without salvage prostate/pelvic radiation or primary radiation (external beam or brachytherapy) * If past prostatectomy, pathologic stage no greater than T1-3, N1, M0 * PSA recurrence with PSAdt \< 18 months. There is no minimum PSA for prostatectomy patients. For patients treated with primary radiation therapy PSA should be greater than 2.0 ng/ml * No evidence of recurrent disease on exam, bone scan, CT/MRI abdomen/pelvis or CXR * Prior ADT allowed if \< 6 months and testosterone recovered to within 50 units (ng/dl) of normal range * ECOG Performance status of 0-1 * Absolute neutrophil count of \>1,500 * Platelet count \> 100,000 * Hg \> 8g/dl * 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 allowed if was \< 6 cycles and \> 6 months prior to study entry * 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 the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-free Survival | 2 years | To identify a difference in relapse-free survival in men treated with short course ADT (6 months) versus short course ADT plus bevacizumab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With PSA <0.2 ng/ml at Six Months | Six months (at completion of treatment) | Number of participants with a PSA \<0.2 ng/ml at six months (upon completion of treatment). |
| Cardiovascular Safety Including Measurement of Blood Pressure During Treatment Period (6 Months). | 6 months | The number of patients who developed hypertension (greater that 150 systolic or greater than 90 diastolic) during treatment period. |
| Analysis of Cytokines and Angiogenic Factors in Plasma/Serum | 6 months | Analysis of cytokines and angiogenic factors in plasma/serum at baseline and at 6 months (end of treatment). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Androgen Deprivation Therapy Plus Bevacizumab Androgen Deprivation Therapy Plus Bevacizumab
Androgen Deprivation Therapy: leuprolide: 22.5mg given IM every 3 months for a total of 6 months or, goserelin acetate: 10.8mg given SC every 3 months for a total of 6 months
bicalutamide: 50mg orally daily for 6 months
bevacizumab: 15mg/ks given IV every three weeks for a total of 8 infusions over 6 months | 66 |
| Androgen Deprivation Therapy Alone Androgen Deprivation Therapy Alone
Androgen Deprivation Therapy: leuprolide: 22.5mg given IM every 3 months for a total of 6 months or, goserelin acetate: 10.8mg given SC every 3 months for a total of 6 months
bicalutamide: 50mg orally daily for 6 months | 36 |
| Total | 102 |
Baseline characteristics
| Characteristic | Androgen Deprivation Therapy Plus Bevacizumab | Androgen Deprivation Therapy Alone | Total |
|---|---|---|---|
| Age, Continuous | 66 years | 63 years | 65 years |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 66 Participants | 36 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 36 | 63 / 66 |
| serious Total, serious adverse events | 5 / 36 | 18 / 66 |
Outcome results
Primary
Relapse-free Survival
To identify a difference in relapse-free survival in men treated with short course ADT (6 months) versus short course ADT plus bevacizumab.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Relapse-free Survival | 13 months |
| Group 2 | Relapse-free Survival | 10 months |
Secondary
Analysis of Cytokines and Angiogenic Factors in Plasma/Serum
Analysis of cytokines and angiogenic factors in plasma/serum at baseline and at 6 months (end of treatment).
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Analysis of Cytokines and Angiogenic Factors in Plasma/Serum | 13755 pg/ml |
| Group 2 | Analysis of Cytokines and Angiogenic Factors in Plasma/Serum | 10179 pg/ml |
Secondary
Cardiovascular Safety Including Measurement of Blood Pressure During Treatment Period (6 Months).
The number of patients who developed hypertension (greater that 150 systolic or greater than 90 diastolic) during treatment period.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Cardiovascular Safety Including Measurement of Blood Pressure During Treatment Period (6 Months). | 48 participants |
| Group 2 | Cardiovascular Safety Including Measurement of Blood Pressure During Treatment Period (6 Months). | 13 participants |
Secondary
Number of Participants With PSA <0.2 ng/ml at Six Months
Number of participants with a PSA \<0.2 ng/ml at six months (upon completion of treatment).
Time frame: Six months (at completion of treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Number of Participants With PSA <0.2 ng/ml at Six Months | 51 Number of participants |
| Group 2 | Number of Participants With PSA <0.2 ng/ml at Six Months | 27 Number of participants |