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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00658697
• Other study ID #: 08-004
• Status: Completed
• Phase: Phase 2
• First received: April 9, 2008
• Last updated: January 29, 2016
• Start date: June 2008
• Est. completion date: June 2015

Study information

• Verified date: January 2016
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 PSA after treatment of their prostate cancer with surgery or radiation)

Description:

A single arm phase 2 study designed to evaluate the rate of patients free from 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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 2015
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• 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
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

Locations

Country	Name	City	State
United States	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

Sponsors (4)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of PSA Progression at 1 Year After Completing 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 were performed at the beginning of every cycle during the treatment, then every 3 months after completion of study therapy	No
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.	1 years + 3 month off last ADT injection	No
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	Clinical assessments were performed at the beginning of every cycle during the treatment, then every 3 months after completion of study therapy	No
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	2 years	No
Secondary	Toxicity	Treatment related adverse events	Assessed each cycle throughout treatment form time of first dose and up to day 30 post-treatment	Yes