Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

AZD2171 in Treating Patients With Metastatic Androgen-Independent Prostate Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Active 18 and over NCI NCI-07-C-0059 NCI-P6964, 7395, NCT00436956

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

Primary

1. Determine if treatment with AZD2171 is associated with a 30% 6-month probability of progression-free survival in patients with metastatic androgen-independent prostate cancer.

Secondary

1. Determine the overall response rate and overall survival of patients treated with this regimen.
2. Assess survival, from the time of prostate-specific antigen (PSA) progression, in the absence of radiological or clinical progression.
3. Assess the biologic effect of this regimen in these patients.
4. Determine the pharmacokinetics of this regimen in these patients.
5. Evaluate the PSA response rate in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed prostate cancer
  • Metastatic disease
  • Progressive, androgen-independent disease
    • Radiographic evidence of disease that has continued to progress despite hormonal agents
      • Patients on flutamide must have disease progression at least 4 weeks after withdrawal
      • Patients on bicalutamide or nilutamide must have disease progression at least 6 weeks after withdrawal
    • Progressive disease requires that a measurable lesion is expanding, new lesions have appeared, and/or that prostate-specific antigen is continuing to rise on successive measurements



• Must have received prior docetaxel for androgen-independent prostate cancer



• Concurrent gonadotropin-releasing hormone agonists or antagonists required for patients without bilateral surgical castration



• No known brain metastases

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from prior therapy, including surgery
• At least 4 weeks since prior agents not approved by the FDA
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or major surgery
• Concurrent bisphosphonates allowed for patients with known bone metastases
• No concurrent grapefruit juice
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents or therapies

Patient Characteristics:

• ECOG performance status (PS) 0-2 Karnofsky PS 60-100%
• Life expectancy > 3 months
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8 g/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to clinical Gilbert’s syndrome)
• AST and ALT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN OR creatinine clearance > 40 mL/min
• Urine protein ≤ +1 on two consecutive dipsticks taken no less than 1 week apart
• Blood pressure < 140/90 mm Hg
• Fertile patients must use effective contraception during and for 3 months after completion of study participation
• No other invasive malignancies within the past 5 years except nonmelanoma skin cancer or noninvasive bladder cancer
• No mean QTc > 470 msec (with Bazett’s correction)
• No history of familial long QT syndrome
• No uncontrolled intercurrent illness including, but not limited to, any of the following:
  • Hypertension
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance

Expected Enrollment

A total of 37 patients will be accrued for this study.

Outcomes

6-month progression-free survival

Prostate-specific antigen
Pharmacokinetics

Outline

Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during course 1 of study therapy. Samples are evaluated for pharmacokinetics and tumor and gene expression alterations. Patients undergo a dynamic contrast-enhanced MRI at baseline and on days 2, 28, and 56 for the evaluation of tumor vascularity.

After the completion of study treatment, patients are followed periodically.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

William Figg, PharmD, Protocol chair		Ph: 301-402-3622 Email: wdfigg@helix.nih.gov
William Dahut, MD, Principal investigator		Ph: 301-435-8183 Email: dahutw@mail.nih.gov
Marcia Mulquin, RN, Study coordinator		Ph: 301-435-5613

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Featured trial article

Registry Information
Official Title		A Phase II Study of AZD2171 in Metastatic Androgen Independent Prostate Cancer
Trial Start Date		2007-05-07
Trial Completion Date		2008-08-09 (estimated)
Registered in ClinicalTrials.gov		NCT00436956
Date Submitted to PDQ		2006-12-27
Information Last Verified		2008-08-29