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

NCT ID: NCT00658697

Last Updated: 2017-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2015-06-30

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel, Bevacizumab, and 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

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)

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles

Bevacizumab

Intervention Type: DRUG

Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles

ADT

Intervention Type: DRUG

Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months)

Bicalutamide

Intervention Type: DRUG

Starting on day 84 orally once daily until hormone therapy is completed

Interventions

Docetaxel

Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles

Intervention Type: DRUG

Bevacizumab

Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles

Intervention Type: DRUG

ADT

Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months)

Intervention Type: DRUG

Bicalutamide

Starting on day 84 orally once daily until hormone therapy is completed

Intervention Type: DRUG

Other Intervention Names

Taxotere, Docecad; Avastin; Lupron or Zoladex; Casodex, Cosudex, Calutide, Kalumid

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Mary-Ellen Taplin, MD

Associate Professor of Medicine, HMS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mary-Ellen Taplin, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

University of Maryland - Greenebaum Cancer Center

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

08-004

Identifier Type: -

Identifier Source: org_study_id