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Docetaxel and Prednisone With or Without Cediranib in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy
This study is ongoing, but not recruiting participants.

First Received on September 7, 2007.   Last Updated on January 23, 2012   History of Changes
Sponsor: Barbara Ann Karmanos Cancer Institute
Collaborator: National Cancer Institute (NCI)
Information provided by: Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00527124
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving docetaxel together with prednisone, with or without cediranib, may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving docetaxel and prednisone together with or without cediranib works in treating patients with metastatic prostate cancer that did not respond to hormone therapy.


Condition Intervention Phase
Prostate Cancer
Drug: cediranib maleate
Drug: docetaxel
Drug: prednisone
Phase II

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Phase II Trial of AZD2171, Docetaxel, and Prednisone Compared to Docetaxel and Prednisone in Patients With Metastatic, Hormone Refractory Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Progression-free survival rate at 6 months [ Time Frame: At 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Prostate-specific antigen (PSA)response duration [ Time Frame: Weeks 4, 7 9 and at end of treatment ] [ Designated as safety issue: No ]
    PSA

  • PSA control duration [ Time Frame: Weeks 4, 7, 10 and at the end of treatment ] [ Designated as safety issue: No ]
    PSA

  • Time to progression [ Time Frame: Every 3 cycles ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From the time of registration date until death from any cause ] [ Designated as safety issue: No ]
  • Levels of the various serum correlative markers and positron emission test (PET) imaging correlates [ Time Frame: Pre-study, Weeks 4 & 7 ] [ Designated as safety issue: No ]
    [F18] FMAU PET & correlative blood and tissue


Estimated Enrollment: 104
Study Start Date: November 2007
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral cediranib once daily on days 1-21, docetaxel IV over 1 hour on day 1, and oral prednisone twice daily on days 1-21.
Drug: cediranib maleate
given orally
Drug: docetaxel
given IV
Drug: prednisone
given orally
Active Comparator: Arm II
Patients receive docetaxel and prednisone as in arm I.
Drug: docetaxel
given IV
Drug: prednisone
given orally

Detailed Description:

OBJECTIVES:

Primary

  • To determine the 6-month progression-free survival rate of patients with hormone refractory metastatic adenocarcinoma of the prostate treated with docetaxel and prednisone with vs without cediranib.

Secondary

  • To evaluate the safety profile of cediranib, docetaxel, and prednisone in patients with metastatic hormone-refractory prostate cancer.
  • To determine the duration of prostate-specific antigen (PSA) response and PSA control in patients with metastatic hormone-refractory prostate cancer treated with cediranib, docetaxel, and prednisone.
  • To determine the partial and complete response rate in patients with measurable disease treated with cediranib, docetaxel, and prednisone.
  • To determine time to progression in patients with metastatic hormone-refractory prostate cancer treated with cediranib, docetaxel, and prednisone.
  • To determine overall survival in patients with metastatic hormone-refractory prostate cancer.
  • To perform correlative marker studies measuring serum levels of VEGF, PDGF, sICAM, bFGF, interleukin (IL)-6, and IL-8.
  • To perform a pilot study of [F18]FMAU positron emission test (PET) imaging on patients receiving cediranib, docetaxel, and prednisone.

OUTLINE: This is a multicenter study. Patients are stratified by participating institution. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral cediranib once daily on days 1-21, docetaxel IV over 1 hour on day 1, and oral prednisone twice daily on days 1-21.
  • Arm II: Patients receive docetaxel and prednisone as in arm I. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Archival paraffin-embedded tissue blocks or slides from time of diagnosis (or subsequent, but prior to therapy) are evaluated for expression of molecular targets relevant to this study. Blood specimens from baseline, after courses 1 and 2, and after completion of study treatment are analyzed for protein markers. Samples are analyzed by ELISA and IHC for angiogenesis-associated plasma proteins, plasma levels of VEGF, tumor expression of PDGFR, and interleukin (IL)-6 and IL-8 plasma levels. Patients also undergo positron emission test (PET) scans utilizing fluorodeoxyglucose (FDG) at baseline and after course 1.

After completion of study treatment, patients are followed every 3 months for 52 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the prostate

    • Clinical/radiologic metastases with objective evidence of disease progression by imaging or by rising prostate-specific antigen (PSA) despite androgen deprivation therapy

      • Rising PSA must be determined based on a rising trend with 2 successive elevations at a minimum interval of 1 week
  • Meets 1 of the following criteria:

    • Measurable disease, with any level of PSA

      • At least 1 unidimensionally measurable lesion (longest diameter to be recorded) ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
    • Nonmeasurable disease

      • PSA ≥ 5 ng/mL OR new areas of bony metastases on bone scan
  • Castrate levels of testosterone < 50 ng/dL must be maintained and documented

    • Luteinizing hormone-releasing hormone (LHRH) agonist therapy must be continued, if required to maintain castrate levels of testosterone
  • No untreated unstable brain or meningeal metastases

    • Patients with radiological evidence of stable brain metastases are eligible provided they are asymptomatic and do not require corticosteroids or have been treated with corticosteroids and show clinical and radiological evidence of stabilization at least 10 days after discontinuation of steroids

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status (PS) ≤ 2 or Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • Leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelet count ≥ 100,000/mcL
  • Total bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Proteinuria ≤ 1+ and urine protein:creatinine ratio ≤ 1.0 OR 24-hour urine protein < 1,000 mg

Exclusion criteria:

  • Peripheral neuropathy ≥ grade 2
  • Uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Congestive heart failure, second or third degree heart block, or recent myocardial infarction within the past 6 months
  • QTc prolongation > 500 msec OR other ECG abnormality noted within 14 days of treatment
  • New York Heart Association class III or IV cardiac disease

    • Class II disease controlled with treatment and monitoring allowed
  • History of poorly controlled hypertension (e.g., resting blood pressure > 150/90 mm Hg with or without hypertensive therapy)
  • History of a curatively treated malignancy with a survival prognosis of less than 5 years or concurrent malignancy except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ
  • History of significant gastrointestinal impairment, as judged by the investigator, that would significantly affect the absorption of cediranib
  • History of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
  • Known hypersensitivity to cediranib or any of its excipients
  • Significant hemorrhage (30 mL bleeding/episode in previous 3 months) or hemoptysis (5 mL fresh blood in previous 4 weeks)
  • Prior enrollment or randomization of treatment in the present study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Patients must be off flutamide antiandrogen therapy for ≥ 4 weeks (6 weeks for bicalutamide or nilutamide)
  • No prior chemotherapy for metastatic prostate cancer
  • No major surgery within the past 14 days or a surgical incision that is not fully healed
  • No HIV-positive patients on combination antiretroviral therapy
  • No conditions requiring concurrent use of drugs or biologics with proarrhythmic potential
  • No other investigational agents within 30 days prior to study enrollment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00527124

Locations
United States, California
UC Davis Cancer Center
Sacramento, California, United States, 95817
United States, Colorado
University of Colorado at Denver and Health Sciences Center
Aurora, Colorado, United States, 80045-0511
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Michigan
St. Joseph Mercy Health System- Ann Arbor
Ann Arbor, Michigan, United States, 48106
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Veterans Affairs Medical Center - Detroit
Detroit, Michigan, United States, 48201
United States, Ohio
Arthur G. James Cancer Hospital and Richard Solove Research Institute/ Ohio State University
Columbus, Ohio, United States, 43210
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
United States, Wisconsin
University of Wisconsin-Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Elisabeth I. Heath, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Patricia M. LoRusso, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00527124     History of Changes
Other Study ID Numbers: CDR0000564449, U01CA062487, P30CA022453, WSU-2007-015
Study First Received: September 7, 2007
Last Updated: January 23, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
stage IV prostate cancer
adenocarcinoma of the prostate

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Docetaxel
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on February 09, 2012