AZD2171 to Treat Prostate Cancer

NCT00436956 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 07005907-C-0059
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• AZD2171 (Cediranib) is an experimental drug that inhibits formation of new blood vessels.
• Tumors need new blood vessels to grow. Preventing the growth of new blood vessels with AZD2171 may inhibit tumor growth. Objectives:
• To determine the effectiveness and side effects of AZD2171 in patients with prostate cancer that has metastasized (spread beyond the primary site). Eligibility:
• Males 18 years of age and older with androgen-independent prostate cancer that has metastasized.
• Patients must have received prior treatment with docetaxel. Design: Patients take one AZD2171 by mouth every day in 28-day treatment cycles and undergo the following procedures:
• 1- to 2-day hospitalization at the start of the study for biopsies and blood measurements to determine the level of AZD2171 in the bloodstream. Blood is drawn immediately before the first dose, and 0.25 hr, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, and 48 hours after the dose is taken.
• Blood tests before starting treatment and then monthly to determine the level of vascular endothelial growth factor receptor ( VEGFR), a protein involved in blood vessel formation.
• Magnetic resonance imaging (MRI) scans once a month to evaluate blood flow.
• Tumor biopsies (optional) both before and after the second and sixth treatment cycles.
• Clinic visits every 4 weeks, including various routine and research blood tests, urine test and electrocardiogram.
• Computed tomography (CT) scan of the chest, abdomen, and pelvis every 8 weeks
• Bone scan every 8 weeks Patients record all doses of AZD2171 taken or missed in a pill diary. They record their blood pressure at least once daily in a blood pressure diary. Treatment may continue as long as the patient tolerates the AZD2171 and the cancer does not worsen. ...

Conditions

Prostate Cancer

Keywords

VEGF; Angiogenesis; Hormone-Refractory; Bone Metastases; Docetaxel-Resistant; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Percent Probability of Participants With 6-month Progression-free Survival (PFS)

  PFS is the proportion of subjects who progress or die by 6 months after the start of the combined therapy. PFS is determined by prostatic specific antigen (PSA) consensus criteria and the Response Evaluation Criteria in Solid Tumors (RECIST). PSA consensus criteria is defined as PSA decline of \>/= 50% or PSA progression. RECIST is defined as the following: Complete response (CR) is disappearance of all target lesions; partial response (PR) is at least a 30% decline in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease ((PD) at least a 20% increase in the sum of the LD of target lesions, or the appearance of one or more lesions), taking as reference the smallest sum LD since the treatment started. Data is estimated and the probability of PFS as a function of time was determined using the Kaplan-Meier method.

  6 months

Secondary Outcomes (6)

• Number of Participants With Adverse Events

  Date treatment consent signed to date off study, approximately 61.5 months

• Number of Grade 2 Toxicities

  61.5 months

• Number of Grade 3 Toxicities

  61.5 months

• Median Overall Survival

  44 months

• Median Progression Free Survival (PFS)

  up to 14.9 months based on a Kaplan-Meier analysis.

Study Arms (1)

AZD2171 in Prostate Cancer

EXPERIMENTAL

Cohort 1 (n=35) received 20 mg AZD2171 (Cediranib) orally daily. Cohort 2 (n=23) received prednisone 10 mg orally daily with 20 mg AZD2171.

Procedure: Magnetic Resonance Imaging (DCE-MRI); Drug: AZD2171; Drug: Prednisone

Interventions

Magnetic Resonance Imaging (DCE-MRI) PROCEDURE

Scans evaluate tumor tissue and blood flow.

Also known as: MRI

AZD2171 in Prostate Cancer

AZD2171 DRUG

20 mg oral daily for 28 days

Also known as: Cediranib

AZD2171 in Prostate Cancer

Prednisone DRUG

10mg orally daily in combination with AZD2171 20mg daily.

Also known as: Deltasone

AZD2171 in Prostate Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histopathological confirmation of prostate cancer by the Laboratory of Pathology of the National Cancer Institute (NCI), Pathology Department of the National Naval Medical Center or Pathology Department of Walter Reed Army Medical Center prior to entering this study. Patients whose pathology specimens are no longer available may be enrolled in the trial if the patient has a clinical course consistent with prostate cancer and available documentation from an outside pathology laboratory of the diagnosis. In cases where original tissue blocks or archival biopsy material is available, all efforts should be made to have the material forwarded to the research team for use in correlative studies.
• Patients must have metastatic progressive androgen-independent prostate cancer. There must be radiographic evidence of disease that has continued to progress despite hormonal agents. Progression requires that a measurable lesion is expanding, new lesions have appeared, and/or that prostatic specific antigen (PSA) is continuing to rise on successive measurements. Patients on flutamide must have disease progression at least 4 weeks after withdrawal. Patients on bicalutamide or nilutamide must have progression at least 6 weeks after withdrawal.
• Patients must have received prior therapy with docetaxel for androgen-independent prostate cancer. Any number of prior treatments are acceptable.
• Age greater than or equal to 18 years.
• Life expectancy of greater than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count greater than or equal to 1,500/mcL
• Platelets greater than or equal to 100,000/mcL
• Hemoglobin greater than or equal to 8 g/dL
• Total bilirubin within normal institutional limits (unless with clinical Gilbert's syndrome)
• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST(SGOT))/alanine aminotransferase/serum glutamic pyruvic transaminase (ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
• Creatinine less than or equal to 1.5 times institutional upper normal institutional limits
• Creatinine clearance greater than 40 mL/min/1.3 m\^2 for patients with creatinin levels above institutional normal as calculated by the Cockcroft Gault formula.
• Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.

You may not qualify if:

• Patients who have had chemotherapy, radiotherapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Patients may not be receiving any agents not approved by the Food and Drug Administration (FDA) within the past four weeks.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Mean QTc greater than 470 msec (with Bazett's correction) in screening electrocardiogram or history of familial long Q wave, T wave (QT) syndrome.
• Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart.
• Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Balbay MD, Pettaway CA, Kuniyasu H, Inoue K, Ramirez E, Li E, Fidler IJ, Dinney CP. Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor. Clin Cancer Res. 1999 Apr;5(4):783-9.

  PMID: 10213213 BACKGROUND

• Beedassy A, Cardi G. Chemotherapy in advanced prostate cancer. Semin Oncol. 1999 Aug;26(4):428-38.

  PMID: 10482185 BACKGROUND

• Belgore FM, Blann AD, Lip GY. Measurement of free and complexed soluble vascular endothelial growth factor receptor, Flt-1, in fluid samples: development and application of two new immunoassays. Clin Sci (Lond). 2001 May;100(5):567-75.

  PMID: 11294698 BACKGROUND

• Huang J, Jochems C, Talaie T, Anderson A, Jales A, Tsang KY, Madan RA, Gulley JL, Schlom J. Elevated serum soluble CD40 ligand in cancer patients may play an immunosuppressive role. Blood. 2012 Oct 11;120(15):3030-8. doi: 10.1182/blood-2012-05-427799. Epub 2012 Aug 28.

  PMID: 22932804 BACKGROUND

• Dahut WL, Madan RA, Karakunnel JJ, Adelberg D, Gulley JL, Turkbey IB, Chau CH, Spencer SD, Mulquin M, Wright J, Parnes HL, Steinberg SM, Choyke PL, Figg WD. Phase II clinical trial of cediranib in patients with metastatic castration-resistant prostate cancer. BJU Int. 2013 Jun;111(8):1269-80. doi: 10.1111/j.1464-410X.2012.11667.x. Epub 2013 Feb 18.

  PMID: 23419134 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Magnetic Resonance Spectroscopy; cediranib; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: William L. Dahut, M.D.
• Organization: National Cancer Institute

dahutw@mail.nih.gov

301-435-8183

Study Officials

• William L Dahut, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: October 16, 2006
• Primary Completion: February 1, 2010
• Study Completion: February 5, 2014
• Last Updated: October 9, 2018
• Results First Posted: July 1, 2014

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)