Study 1 of 1 for search of: A Randomized, Phase II Trial of AZD2171 (Cediranib), Docetaxel, and Prednisone
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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 currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2010
First Received: September 7, 2007   Last Updated: February 2, 2010   History of Changes
Sponsor: Barbara Ann Karmanos Cancer Institute
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
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: Treatment, Randomized
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 National Cancer Institute (NCI):

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

Secondary Outcome Measures:
  • Prostate-specific antigen (PSA) response duration [ Designated as safety issue: No ]
  • PSA control duration [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Levels of the various serum correlative markers and positron emission test (PET) imaging correlates [ Designated as safety issue: No ]

Estimated Enrollment: 104
Study Start Date: November 2007
Estimated Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Experimental
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
Arm II: Active Comparator
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, Colorado
University of Colorado Cancer Center at UC Health Sciences Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Clinical Trials Office - University of Colorado Cancer Center     720-848-0650        
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Clinical Trials Office - Greenebaum Cancer Center at Universit     800-888-8823        
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Clinical Trials Office - Barbara Ann Karmanos Cancer Institute     313-576-9363        
Breslin Cancer Center at Ingham Regional Medical Center Recruiting
Lansing, Michigan, United States, 48910
Contact: Clinical Trials Office - Breslin Cancer Center at Ingham Regio     517-334-2765        
Saint Joseph Mercy Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48103
Contact: Contact Person     734-712-5658        
Sinai-Grace Hospital Recruiting
Detroit, Michigan, United States, 48235
Contact: Elisabeth Heath     313-576-8717        
Veterans Affairs Medical Center - Detroit Recruiting
Detroit, Michigan, United States, 48201
Contact: Contact Person     313-576-1000        
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Ohio State University Cancer Clinical Trial Matching Service     866-627-7616     osu@emergingmed.com    
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Recruiting
Madison, Wisconsin, United States, 53792-6164
Contact: Clinical Trials Office - University of Wisconsin Paul P. Carbo     608-262-5223        
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: Barbara Ann Karmanos Cancer Institute ( Patricia M. LoRusso )
Study ID Numbers: CDR0000564449, WSU-2007-015
Study First Received: September 7, 2007
Last Updated: February 2, 2010
ClinicalTrials.gov Identifier: NCT00527124     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV prostate cancer
adenocarcinoma of the prostate

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

ClinicalTrials.gov processed this record on February 08, 2010