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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.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00527124
First received: September 7, 2007
Last updated: February 7, 2014
Last verified: December 2013
  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. 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.


Condition Intervention Phase
Adenocarcinoma of the Prostate
Stage IV Prostate Cancer
Drug: cediranib maleate
Drug: docetaxel
Drug: prednisone
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel 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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • 6-month Progression-free Survival (PFS) Proportion [ Time Frame: Followed for 52 weeks at 3 month intervals after coming off treatment, time period equal to the length of treatment + up to 12 months ] [ Designated as safety issue: No ]
    The proportion of patients on each treatment arm who survive ≥ 6.00 months progression-free


Secondary Outcome Measures:
  • Prostate-specific Antigen (PSA) Response and PSA Control Duration in Accordance With the Prostate Specific Antigen Working Group [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
    Will be analyzed with standard Kaplan-Meier (K-M) methodology. Both point and 95% CI estimates of the median and other statistics (e.g., the 3-month rate, 6-month rate, etc.) will be computed from the censored distribution of each of these two TTE endpoints.

  • Partial and Complete Response Rate Evaluated by the RECIST Criteria [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
    Will be analyzed with standard Kaplan-Meier (K-M) methodology. Both point and 95% CI estimates of the median and other statistics (e.g., the 3-month rate, 6-month rate, etc.) will be computed from the censored distribution of each of these two TTE endpoints.

  • Time to Progression [ Time Frame: The time from registration date until documented clinical disease progression, or until date of death, whichever occurs first, assessed up to 52 weeks ] [ Designated as safety issue: No ]
    Analyzed with standard K-M methodology. Both point and 95% CI estimates of the median and other statistics (e.g., the 3-month rate, 6-month rate, etc.) will be computed from the censored distribution of TTP. These point and CI estimates will be reported for all patients combined, and separately for each treatment arm.

  • Overall Survival [ Time Frame: The time from registration date until death from any cause, assessed up to 52 weeks ] [ Designated as safety issue: No ]
    Analyzed with standard K-M methodology.


Enrollment: 84
Study Start Date: November 2007
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
Other Names:
  • AZD2171
  • Recentin
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: prednisone
Given orally
Other Names:
  • DeCortin
  • Deltra
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II
Patients receive docetaxel and prednisone as in arm I.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: prednisone
Given orally
Other Names:
  • DeCortin
  • Deltra
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVE:

I. 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 OBJECTIVES:

I. To evaluate the safety profile of cediranib, docetaxel, and prednisone in patients with metastatic hormone-refractory prostate cancer.

II. 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.

III. To determine the partial and complete response rate in patients with measurable disease treated with cediranib, docetaxel, and prednisone.

IV. To determine time to progression in patients with metastatic hormone-refractory prostate cancer treated with cediranib, docetaxel, and prednisone.

V. To determine overall survival in patients with metastatic hormone-refractory prostate cancer.

VI. To perform correlative marker studies measuring serum levels of VEGF, PDGF, sICAM, bFGF, interleukin (IL)-6, and IL-8.

VII. 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

Inclusion Criteria:

  • 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
  • Total bilirubin normal
  • 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
  • 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
  • Histologically confirmed adenocarcinoma of the prostate
  • 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
  • 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
  • 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
  • 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
  • No untreated unstable brain or meningeal metastases
  • Known hypersensitivity to cediranib or any of its excipients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00527124

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Wayne State University
Detroit, Michigan, United States, 48202
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Elisabeth Heath Wayne State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00527124     History of Changes
Other Study ID Numbers: NCI-2009-00174, NCI-2009-00174, 2007-015, CDR0000564449, 2007-015, 7451, N01CM00038, U01CA062491, P30CA022453, U01CA062487
Study First Received: September 7, 2007
Results First Received: July 9, 2013
Last Updated: February 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Cediranib
Docetaxel
Prednisone
Anti-Inflammatory Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 24, 2014