Neoadjuvant Bevacizumab Plus Docetaxel in High Risk Patients With Prostate Cancer Undergoing Radical Prostatectomy

Prostate Cancer Clinical Trial

Official title:

A Phase II Study of Neoadjuvant Bevacizumab Plus Docetaxel in High Risk Patients With Prostate Cancer Undergoing Radical Prostatectomy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00321646
• Other study ID #: 05-438
• Status: Completed
• Phase: Phase 2
• First received: May 2, 2006
• Last updated: November 6, 2013
• Start date: June 2006
• Est. completion date: December 2012

Study information

• Verified date: November 2013
• 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

The main purpose of this trial is to collect information and to evaluate the effects, good or bad, the combination of docetaxel and bevacizumab has on patients with high risk prostate cancer that are undergoing radical prostatectomy.

Description:

• Patients who are eligible for this study will undergo an endorectal MRI scan test before beginning the research study.

• After the MRI, the patient will begin the docetaxel plus bevacizumab part of the study. Each treatment cycle starts on the day you receive both drugs and lasts 21 days. Patients will undergo a total of 6 cycles-5 with docetaxel plus bevacizumab and one with docetaxel alone.

• At the beginning of each cycle, the patient will come into the clinic for a visit that will last about 3 hours. The following will happen at these visits: physical examination including vital signs and rectal exam; questions about the patients health and the medications they are taking; blood tests (both routine and research blood tests); urine tests; bevacizumab infusion; docetaxel infusion.

• The patients first dose of bevacizumab will be given on Day 1 of the first cycle over 90 minutes. If the patient tolerates the 90-minute infusion well, later doses may be given over a shorter period of time.

• The day before and the morning of the beginning of each cycle, the patient will be given a steroid called dexamethasone in pill form to help decrease the side effects of the treatment.

• The above tests and procedures will be repeated every 21 days a total of five times. For the sixth time, the patient will have all the same tests and procedures except they will not receive bevacizumab.

• After the six cycles, the patient will undergo another endorectal MRI.

• One to two months after finishing the sixth cycle, the patient will undergo a radical prostatectomy to remove their prostate.

• Two to three months after the surgery the patient will return to the clinic to have the following tests and procedures: questions about the patient's health; routine blood tests and research blood tests.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: December 2012
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological documentation of adenocarcinoma of the prostate, with available biopsy pathology. Material from this biopsy must be available for central review at DF/HCC by the beginning of the second cycle of therapy.

• Potential candidate for radical prostatectomy

• Must meet one or more of the below characteristics: Gleason score of 8, 9 or 10; serum PSA of greater than or equal to 20 ng/mL; clinical T stage of T3; PSA velocity of greater than or equal to 2ng/mL/year in the year prior to diagnosis; Gleason score of 7 and erMRI T3 disease; Greater than or equal to 50% of the total number of biopsy cores positive for prostate cancer and either PSA > 10ng/mL or Gleason score of 7 or clinical T stage of T2a, T2b or T2c.

• Greater than six weeks since any major surgery

• Serum testosterone > 100ng/dL

• ECOG Performance Status of 0 or 1

• ANC > 1,500/ul

• Platelets > 100,000/ul

• Total bilirubin, alkaline phosphatase, AST and ALT within normal limits

• Creatinine < 2.0 x upper limit of normal

Exclusion Criteria:

• History of prior radiation, surgery or hormonal therapy treatment for prostate cancer

• Clinical evidence of metastatic prostate cancer

• Ongoing oral steroid use

• Pre-existing neuropathy of grade 2 or greater

• Severe claustrophobia, inability to lie still in a magnet for 60 minutes, a pacemaker, or any other condition that would preclude proximity to a strong magnet.

• History of the following conditions: unstable angina; symptomatic, clinically significant peripheral vascular disease; NY Heart Association Grade 2 or greater heart failure; uncontrolled hypertension; myocardial infarction or stroke < 12 months prior to enrollment; uncontrolled hypertension; active, uncontrolled infection; history of DVT, PE or known coagulopathy or bleeding diathesis; ongoing us of anticoagulant therapy; history of abdominal fistulas, GI perforation, or intra-abdominal abscess within 6 months prior to study entry; non-healing ulcer or fracture; history of another malignancy diagnosed within the last five years; spot urine protein: creatinine ratio > 1.0 at screening.

Study Design

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Bevacizumab
Bevacizumab (marketed as Avastin, Genentech) is an antibody to all isoforms of vascular endothelial growth factor and is the first putative anti-angiogenic agent approved by the Food and Drug Administration (FDA) for the treatment of cancer.All subjects will be treated with intravenous docetaxel and bevacizumab for 5 cycles, followed by docetaxel alone for Cycle 6. Bevacizumab will be given first, at a starting dose of 15 mg/kg. Bevacizumab will be given once every 21 days in the infusion center.
• Docetaxel
Docetaxel will be given intravenously once every 21 days in the infusion center. The starting dose is 70mg/square meter.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (5)

Lead Sponsor	Collaborator
Mary-Ellen Taplin, MD	Beth Israel Deaconess Medical Center, Duke University, Genentech, Inc., Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endorectal MRI Response After Completion of 6 Cycles of Neoadjuvant Therapy	A response was defined as a decrease in tumor size of >50% for the largest lesion in the prostate by endorectal MRI.	after 6 months of neoadjuvant chemotherapy.	No
Secondary	PSA Response After Completing 6 Cycles of Neoadjuvant Chemotherapy.	The rate of PSA decline by 50% compared to baseline PSA.	after 6 months of ajuvant chemotherapy.	No