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A Phase 1 Study of AZD2171 and WBRT in Patients With Brain Metastases

Phase 1
18 Years
Not Enrolling
Male Breast Cancer, Stage IV Breast Cancer, Stage IV Melanoma, Stage IV Non-small Cell Lung Cancer, Stage IV Renal Cell Cancer, Stage IVA Colon Cancer, Stage IVA Rectal Cancer, Stage IVB Colon Cancer, Stage IVB Rectal Cancer, Tumors Metastatic to Brain

Thank you

Trial Information

A Phase 1 Study of AZD2171 and WBRT in Patients With Brain Metastases


I. To determine the safety and tolerability (maximum tolerated dose, or MTD) of AZD2171 when
combined with WBRT in patients with brain metastases.


I. To describe the objective response rate (ORR) in the central nervous system (CNS),
neurologic progression-free survival (N-PFS), overall survival, and cause of death, and to
explore the vascular normalization window using serial, noninvasive imaging parameters.


Patients receive oral cediranib maleate on day 1. Patients undergo whole-brain radiotherapy
5 days a week for 3 weeks beginning on day 3. Treatment continues treatment in the absence
of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

- Patients must have one of the following histologically or cytologically confirmed
cancers diagnosed no less than 12 weeks prior to study enrollment: non-small cell
lung cancer, breast cancer, melanoma, colorectal cancer, or renal cell cancer

- Patients must have >= 1 radiologically proven (by gadolinium-enhanced [Gd-] MRI)
parenchymal brain metastasis

- Patients must have had no prior therapy for brain metastases with the exception of
craniotomy for resection of brain metastases within 8 weeks of study entry

- At least 2 weeks since last prior radiotherapy or chemotherapy (6 weeks if the last
regimen included nitrosoureas, mitomycin C or bevacizumab)

- At least 4 weeks since last surgery

- There is no limit to the number of extracranial sites of disease

- Karnofsky performance status >= 70%

- Life expectancy of greater than 8 weeks

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin =< 1.5 x upper limit of reference range (ULRR)

- AST (SGOT)/ALT (SGPT) =< 2.5 x ULRR or =< 5 x ULRR for patients with liver metastases

- Creatinine =< 1.5 x ULRR or creatinine clearance >= 50 mL/min calculated by
Cockcroft-Gault for patients with creatinine levels > 1.5 x ULRR

- Patients must have a mini-mental status exam (MMSE) score >= 15

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; women of child-bearing potential must have a
negative pregnancy test prior to study entry; should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
nitrosoureas, mitomycin C or bevacizumab) prior to entering the study or those who
have not recovered from adverse events due to agents administered more than 2 weeks

- Patients receiving any other investigational agents or who have participated in an
investigational therapeutic trial within the past 30 days

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to AZD2171

- Patients taking enzyme-inducing antiepileptic drugs (EIAED); patients may be on
non-enzyme-inducing antiepileptic drugs (NEIAED) or may be on no antiepileptic drugs
(AED); patients off EIAED for >= 2 weeks are eligible

- Although the following medications are not contra-indicated on this study, each
should be used with extreme caution, due to potential nephrotoxic effects:
vancomycin, amphotericin, pentamidine

- Patients who have leptomeningeal disease as the only site of CNS involvement are
excluded, because disease progression is difficult to evaluate and standard treatment
options and the extent of radiation may differ

- Patients taking oral anticoagulant drugs are excluded; patients may be taking low
molecular weight heparin

- Patients with a mean corrected QT interval > 470 milliseconds (with Bezett's
correction) or patients with familial prolonged QT syndrome

- Patients with > 1+ proteinuria on two successive urine dipstick assessments taken no
less than 7 days apart, unless urinary protein is < 1.5 g in a 24-hour period; if
first urinalysis shows no protein, then a repeat urinalysis is NOT required

- Patients with significant hemorrhage (> 30mL bleeding per episode in previous 3
months) or hemoptysis (> 5mL fresh blood in previous 4 weeks)

- Patients who have brain imaging (CT or MRI) evidence of acute intra- or peri- tumoral
hemorrhage > grade 1; patients with punctuate hemorrhage or hemosiderin deposition
are eligible

- Patients who cannot undergo MRI safely

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, uncontrolled hypertension (> 140 systolic or > 90 diastolic mm Hg), New
York Heart Association class III or IV heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements

- Patients with conditions requiring concurrent drugs or biologics with proarrhythmic

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with AZD2171

- HIV-positive patients on combination antiretroviral therapy are ineligible

Type of Study:


Study Design:

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

Outcome Measure:

MTD defined as the dose at which no patients develop treatment-related grade 5 toxicity and less than 30% of patients develop acute dose limiting toxicities (DLT) assessed using NCI CTCAE version 4.0

Outcome Time Frame:

7 weeks

Safety Issue:


Principal Investigator

April Eichler

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

August 2009

Completion Date:

Related Keywords:

  • Male Breast Cancer
  • Stage IV Breast Cancer
  • Stage IV Melanoma
  • Stage IV Non-Small Cell Lung Cancer
  • Stage IV Renal Cell Cancer
  • Stage IVA Colon Cancer
  • Stage IVA Rectal Cancer
  • Stage IVB Colon Cancer
  • Stage IVB Rectal Cancer
  • Tumors Metastatic to Brain
  • Breast Neoplasms
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Renal Cell
  • Lung Neoplasms
  • Melanoma
  • Neoplasm Metastasis
  • Breast Neoplasms, Male



Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114