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

Phase 2

Completed

Conditions: Prostate Cancer

Interventions: Drug: Docetaxel
Drug: Bevacizumab
Drug: ADT
Drug: Bicalutamide

Registration Number: NCT00658697

Lead Sponsor: Dana-Farber Cancer Institute

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 42

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Docetaxel, Bevacizumab, and ADT	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)
Docetaxel, Bevacizumab, and ADT	Bicalutamide	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)
Docetaxel, Bevacizumab, and ADT	Docetaxel	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)
Docetaxel, Bevacizumab, and ADT	Bevacizumab	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)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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
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
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.

Trial Locations

Locations (3): University of Maryland - Greenebaum Cancer Center
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Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States
Dana-Farber Cancer Institute
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Boston, Massachusetts, United States