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

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ClinicalTrials.gov Identifier: NCT00658697
Recruitment Status : Completed
First Posted : April 15, 2008
Results First Posted : August 26, 2015
Last Update Posted : May 25, 2017
Sponsor:
Collaborators:
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Genentech, Inc.
Information provided by (Responsible Party):
Mary-Ellen Taplin, MD, 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)

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Docetaxel Drug: Bevacizumab Drug: ADT Drug: Bicalutamide Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : June 2008
Actual Primary Completion Date : September 2014
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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)

Drug: Docetaxel
Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles
Other Name: Taxotere, Docecad

Drug: Bevacizumab
Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles
Other Name: Avastin

Drug: ADT
Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months)
Other Name: Lupron or Zoladex

Drug: Bicalutamide
Starting on day 84 orally once daily until hormone therapy is completed
Other Name: Casodex, Cosudex, Calutide, Kalumid




Primary Outcome Measures :
  1. Prostate-Specific Antigen (PSA) Progression at 1 Year After Completing Androgen Deprivation Therapy (ADT) [ Time Frame: 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 :
  1. Proportion of Patients With PSA Responses at One Year After the Completion of ADT [ Time Frame: 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.

  2. Time to PSA Progression (TTP) [ Time Frame: 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

  3. Testosterone Recovery [ Time Frame: 2 years ]
    Testosterone recovery was defined as >100 or within DFCI institute normal range (240-950) at one year after the completion of ADT

  4. Toxicity [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00658697


Locations
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United States, Maryland
University of Maryland - Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Genentech, Inc.
Investigators
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Principal Investigator: Mary-Ellen Taplin, MD Dana-Farber Cancer Institute

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Responsible Party: Mary-Ellen Taplin, MD, Associate Professor of Medicine, HMS, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00658697     History of Changes
Other Study ID Numbers: 08-004
First Posted: April 15, 2008    Key Record Dates
Results First Posted: August 26, 2015
Last Update Posted: May 25, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute:
Rising PSA
androgen deprivation
bevacizumab (avastin)
docetaxel
lupron
zoladex
bicalutamide
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Bevacizumab
Docetaxel
Bicalutamide
Goserelin
Androgens
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Androgen Antagonists
Hormone Antagonists