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Docetaxel, Bevacizumab and Androgen Deprivation Therapy After Definitive Local Therapy for Prostate Cancer

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Docetaxel
Bevacizumab
ADT
Bicalutamide
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Rising PSA, androgen deprivation, bevacizumab (avastin), docetaxel, lupron, zoladex, bicalutamide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Maryland - Greenebaum Cancer Center
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Docetaxel, Bevacizumab, and ADT

Arm Description

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 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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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 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
Testosterone Recovery
Testosterone recovery was defined as >100 or within DFCI institute normal range (240-950) at one year after the completion of ADT
Toxicity
Treatment related adverse events were graded based on CTCAE v. 3.0.

Full Information

First Posted
April 9, 2008
Last Updated
April 27, 2017
Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00658697
Brief Title
Docetaxel, Bevacizumab and Androgen Deprivation Therapy After Definitive Local Therapy for Prostate Cancer
Official Title
A Phase II Trial of Avastin, Docetaxel and Androgen Deprivation Followed by Continued Avastin and Androgen Deprivation for Men With a Rising Prostate Specific Antigen (PSA) After Local Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 PSA response (< 0.2 ng/mL and < 0.01) at completion of docetaxel/bevacizumab, at completion of ADT and one year off ADT Correlation of PSA response and TTP Toxicity 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Rising PSA, androgen deprivation, bevacizumab (avastin), docetaxel, lupron, zoladex, bicalutamide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Docetaxel, Bevacizumab, and ADT
Arm Type
Experimental
Arm Description
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 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)
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Taxotere, Docecad
Intervention Description
Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles
Intervention Type
Drug
Intervention Name(s)
ADT
Other Intervention Name(s)
Lupron or Zoladex
Intervention Description
Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months)
Intervention Type
Drug
Intervention Name(s)
Bicalutamide
Other Intervention Name(s)
Casodex, Cosudex, Calutide, Kalumid
Intervention Description
Starting on day 84 orally once daily until hormone therapy is completed
Primary Outcome Measure Information:
Title
Prostate-Specific Antigen (PSA) Progression at 1 Year After Completing Androgen Deprivation Therapy (ADT)
Description
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
Secondary Outcome Measure Information:
Title
Proportion of Patients With PSA Responses at One Year After the Completion of ADT
Description
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
Title
Time to PSA Progression (TTP)
Description
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
Title
Testosterone Recovery
Description
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
Title
Toxicity
Description
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

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary-Ellen Taplin, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland - Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Docetaxel, Bevacizumab and Androgen Deprivation Therapy After Definitive Local Therapy for Prostate Cancer

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