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Prostate CancerPhase 2NCT00436956

AZD2171 to Treat Prostate Cancer

A Phase 2 study testing Magnetic Resonance Imaging (DCE-MRI), AZD2171 and Prednisone in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Magnetic Resonance Imaging (DCE-MRI), AZD2171 and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
1 siteUnited States
Study dates
16 Oct 2006to 5 Feb 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%).
Show all 21Show fewer
  • 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
  • OR
  • 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.
  • All patients who have not undergone bilateral surgical castration must continue suppression of testosterone production by appropriate usage of gonadotropin releasing hormone (GnRH) agonists or antagonists.
  • Patients must not have other invasive malignancies (within the past three years with the exception of non-melanoma skin cancers or non-invasive bladder cancer).
  • AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling. Enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 3 months after the end of the treatment.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Patients must have a blood pressure of less than 140/90 at the time of enrollment. Details of antihypertensive treatment, if required, will be left up to the primary care physician.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase II Study of AZD2171 in Metastatic Androgen Independent Prostate Cancer

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.
Read more

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.

...

Read the detailed description

Background:

  • AZD2171 (Cediranib) is an oral potent inhibitor of receptor tyrosine kinases which impact vascular endothelial growth factor-A (VEGF).
  • VEGF appears important in blood vessel formation and disease progression in prostate cancer.
  • No known effective therapy in patients with progressive androgen-independent prostate cancer after treatment with docetaxel.

Objectives:

  • Primary objective of this study is to determine if AZD2171 is associated with a 30% 6 month probability of progression free survival in patients with metastatic androgen independent prostate cancer (AIPC) as determined by clinical and radiographic criteria.
  • Secondary objective of this study will be demonstration of biologic effect by the drug in the patient and on the tumor (when possible). Correlative studies will be conducted on serially obtained tissue biopsies and white blood cell collections.
  • Laboratory correlates will include elucidation of activation of components of the VEGFR2 and angiogenesis pathways and evaluation of endothelial cell adhesion molecules (released by damaged cells) using enzyme-linked immunosorbent assay (ELISA), pharmacogenetic analysis of kinase insert domain receptor (KDR) variants and single nucleotide polymorphisms, and pharmacokinetic characterization of AZD2171 activity.

Eligibility:

  • Metastatic progressive androgen-independent prostate cancer.
  • Prior treatment with docetaxel.
  • May not have corrected QT interval (QTc ) greater than 470 msec or greater than 1+ proteinuria on 2 consecutive dipsticks no less than 1 week apart.

Design:

  • Phase II trial with a two stage design. 12 patients enrolled in first cohort, if 2 or more are progression free at 6 months than enroll up to 35 evaluable patients. The ceiling will be set at 37 to allow for inevaluable patients.
  • Starting dose 20 mg QD (every day) for all patients.
  • Once two stage design is complete then prednisone 10 mg once per day will be given in combination with AZD2171. The total number of patients will be 23 for this portion of the protocol.
Conditions
Prostate Cancer
Being tested
Magnetic Resonance Imaging (DCE-MRI), AZD2171, Prednisone
Keywords
VEGF, Angiogenesis, Hormone-Refractory, Bone Metastases, Docetaxel-Resistant, Prostate Cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Magnetic Resonance Imaging (DCE-MRI)Procedure or surgery

    Also called MRI

    Scans evaluate tumor tissue and blood flow.

  • AZD2171Drug

    Also called Cediranib

    20 mg oral daily for 28 days

  • PrednisoneDrug

    Also called Deltasone

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

Study groups in NCT00436956
Study groupRoleWhat they receive
AZD2171 in Prostate CancerExperimentalCohort 1 (n=35) received 20 mg AZD2171 (Cediranib) orally daily. Cohort 2 (n=23) received prednisone 10 mg orally daily with 20 mg AZD2171.
Receives: Procedure: Magnetic Resonance Imaging (DCE-MRI); Drug: AZD2171; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months

Secondary outcomes (6)

  1. Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

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

  2. Number of Grade 2 Toxicities

    Here is the number of Grade 2 (moderate) toxicities.

    Measured: 61.5 months

  3. Number of Grade 3 Toxicities

    Here is the number of Grade 3 (severe) toxicities.

    Measured: 61.5 months

  4. Median Overall Survival

    Time from treatment start date until date of death or date last known alive.

    Measured: 44 months

  5. Median Progression Free Survival (PFS)

    Time interval from start of treatment to documented evidence of disease progression.

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

  6. Response Per the Response Evaluation Criteria in Solid Tumors (RECIST)

    Response was evaluated by the RECIST. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

    Measured: Every 2 cycles (approximately 56 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2007 (estimated)
  2. Study start16 Oct 2006
  3. Primary completion1 Feb 2010
  4. Study completion5 Feb 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00436956
Sponsor's protocol ID
070059
Other IDs
07-C-0059
Status last verified
Oct 2018
First submitted
15 Feb 2007
Last updated
9 Oct 2018
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 10213213

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

    PubMed 10482185

  • 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.

    PubMed 11294698

  • 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.

    PubMed 22932804

  • 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.

    PubMed 23419134

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Magnetic Resonance Imaging (DCE-MRI), AZD2171 and Prednisone in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Probability of Participants With 6-month Progression-free Survival (PFS) (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00436956, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2018.

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