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

Alternate Title

AZD2171 in Treating Patients With Recurrent Glioblastoma Multiforme

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI MGH-05-254 NCI-7105, 7105, NCT00305656

Objectives

Primary

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

Secondary

1. 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.
2. 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.
3. 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.
4. 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.
5. Determine the overall survival of patients with recurrent GM treated with AZD2171.
6. Determine the radiographic response rate in patients with recurrent GM treated with AZD2171.
7. Determine the safety of AZD2171 in this patient population.

Entry Criteria

Disease Characteristics:

• Histologically confirmed glioblastoma multiforme



• 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

Prior/Concurrent Therapy:

• See Disease Characteristics
• 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

Patient Characteristics:

• Karnofsky performance status ≥ 60%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• 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
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8 g/dL
• Bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• 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

Expected Enrollment

A total of 31 patients will be accrued for this study.

Outcomes

Progression-free survival at 6 months

Response
Overall survival
Toxicity

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.

Trial Contact Information

Trial Lead Organizations

Massachusetts General Hospital

Tracy Batchelor, MD, MPH, Protocol chair		Ph: 617-643-1938; 877-726-5130

Registry Information
Official Title		A Phase II Study of AZD2171 in Recurrent Glioblastoma
Trial Start Date		2005-12-21
Registered in ClinicalTrials.gov		NCT00305656
Date Submitted to PDQ		2005-11-17
Information Last Verified		2007-01-04
NCI Grant/Contract Number		CA117079