AZD2171 in Treating Patients With Recurrent Glioblastoma Multiforme

Adult Glioblastoma Clinical Trial

Official title:

A Phase II Study of AZD2171 in Recurrent Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00305656
• Other study ID #: NCI-2009-00127
• Secondary ID: 05-254N02CO12400
• Status: Completed
• Phase: Phase 2
• First received: March 21, 2006
• Last updated: August 14, 2013
• Start date: January 2006

Study information

• Verified date: July 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase II trial is studying how well AZD2171 works in treating patients with recurrent glioblastoma multiforme. AZD2171 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

Description:

PRIMARY OBJECTIVE:

I. Determine the proportion of patients with recurrent glioblastoma multiforme (GM) who are alive and progression free 6 months after starting AZD2171 therapy.

SECONDARY OBJECTIVES:

I. Assess the biological effect of AZD2171 by using the following MRI techniques: dynamic contrast-enhanced imaging; arterial spin-labeling imaging; perfusion-weighted imaging; and diffusion- tensor imaging at serial time points.

II. Measure circulating endothelial and progenitor cells and plasma levels of tumstatin, (vascular endothelial growth factor (VEGF)-A and -D, sVEGF receptors, P1GF, platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, Ang1, thrombospondin-1, and interleukin-8 as markers for response to antiangiogenic therapy in recurrent GM.

III. Correlate treatment outcomes with pre-AZD2171 tumor specimens with respect to microvascular density, basement membrane and pericyte coverage, and angiopoietin-1 and -2 expression to determine whether these immunohistochemical analyses can be predictive of the response to AZD2171.

IV. Measure polymorphisms of kdr/flk-1 gene and genetic analysis of HIF1-alpha, TP53, and endothelial nitric oxide synthase genes in the archival tumor specimens.

V. Determine the overall survival of patients with recurrent GM treated with AZD2171.

VI. Determine the radiographic response rate in patients with recurrent GM treated with AZD2171.

VII. Determine the safety of AZD2171 in this patient population.

OUTLINE: This is a multicenter study.

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

After completion of study treatment, patients are followed periodically for up to 12 months.

Other known NCT identifiers

• NCT00254943

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Criteria:

• AST/ALT =< 2.5 times upper limit of normal

• Creatinine normal OR creatinine clearance >= 60 mL/min

• Measurable contrast-enhancing tumor >= 1 cm in longest diameter by baseline MRI or CT scan:

• Patient must have been on no steroids OR a stable dose of steroids for >= 5 days prior to baseline MRI or CT scan

• Patients who are on steroids must be maintained on a stable corticosteroid regimen from baseline scan until the start of study treatment

• No intratumoral or peritumoral hemorrhage by MRI

• Karnofsky performance status >= 60%

• No other concurrent malignancy within the past 5 years except curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast

• Mini-mental status examination score >= 15

• Histologically confirmed glioblastoma multiforme

• Platelet count >= 100,000/mm3

• Hemoglobin >= 8 g/dL

• Bilirubin normal

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171

• Mean QTc =< 470 msec (with Bazett's correction) on screening electrocardiogram

• No history of familial long QT syndrome

• No greater than +1 proteinuria on 2 consecutive dipsticks taken >= 1 week apart unless first urinalysis shows no protein

• 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/social situations that would limit compliance with study requirements

• No known coagulopathy that increases the risk of bleeding

• No history of clinically significant hemorrhages

• Recovered from toxicity of prior therapy

• At least 3 months since prior radiation therapy, including cranial radiation therapy

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

• At least 3 weeks since prior molecularly-targeted agents

• At least 4 weeks since prior major surgery

• No more than 2 prior chemotherapy regimens or antineoplastic drugs

• More than 30 days since prior participation in an investigational trial

• At least 2 weeks since prior enzyme-inducing antiepileptic drugs (EIAEDs)

• No concurrent EIAEDs; Concurrent non-EIAEDs allowed

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent investigational agents

• No concurrent vascular endothelial growth factor inhibitors:

Prior thalidomide or lenolidomide allowed

• No concurrent anticoagulants (e.g., warfarin) or antiplatelet agents including aspirin

• No other concurrent anticancer agents or therapies

• No concurrent grapefruit juice

• WBC >= 3,000/mm3

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Absolute neutrophil count >= 1,500/mm3

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Glioblastoma
• Gliosarcoma
• Recurrent Adult Brain Tumor

Intervention

Drug:
• cediranib maleate
Given orally

Locations

Country	Name	City	State
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Batchelor TT, Duda DG, di Tomaso E, Ancukiewicz M, Plotkin SR, Gerstner E, Eichler AF, Drappatz J, Hochberg FH, Benner T, Louis DN, Cohen KS, Chea H, Exarhopoulos A, Loeffler JS, Moses MA, Ivy P, Sorensen AG, Wen PY, Jain RK. Phase II study of cediranib, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients alive and progression-free at 6 months		6 months	No
Secondary	Radiographic response proportion	Will be described with 95% confidence limits.	Up to 12 months	No
Secondary	Overall survival	Will be described with 95% confidence limits.	Up to 12 months	No
Secondary	Toxicity proportion	Will be described with 95% confidence limits.	Up to 12 months	Yes