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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

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Adenocarcinoma of the Prostate; Stage IV Prostate Cancer

Intervention: cediranib maleate (Drug); docetaxel (Drug); prednisone (Drug); laboratory biomarker analysis (Other)

Phase: Phase 2

Status: Terminated

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Elisabeth Heath, Principal Investigator, Affiliation: Wayne State University

Summary

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 6-month Progression-free Survival (PFS) Proportion

Secondary outcome:

Prostate-specific Antigen (PSA) Response and PSA Control Duration in Accordance With the Prostate Specific Antigen Working Group

Partial and Complete Response Rate Evaluated by the RECIST Criteria

Time to Progression

Overall Survival

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

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

Locations and Contacts

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201, United States

Wayne State University, Detroit, Michigan 48202, United States

M D Anderson Cancer Center, Houston, Texas 77030, United States

University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, United States

Additional Information

Starting date: November 2007
Last updated: March 25, 2015

Page last updated: August 23, 2015

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