AZD2171 and Whole Brain Radiation Therapy (WBRT) in Patients With Brain Metastases - Full Text View

Sponsor:	Massachusetts General Hospital
Collaborators:	Dana-Farber Cancer Institute National Cancer Institute (NCI)
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00937482

Purpose

In this research study the investigators are looking for the highest dose of AZD2171 that can be given safely to participants with brain metastases who are being treated with whole brain radiation. The investigators also want to see what side effects participants experience when taking AZD2171. The researchers are looking at the effect of this drug on the participants's tumor size and disease progression. This drug works by interfering with (or inhibiting) a substance called VEGF (Vascular Endothelial Growth Factor). VEGF helps tumors grow and survive by supporting the growth of the blood vessels that bring nutrients to the tumor. When the activity of VEGF is interrupted, the blood vessels around the tumor cells die. The tumors may then die because nutrients aren't getting to the tumor.

Condition	Intervention	Phase
Brain Metastases Lung Cancer Breast Cancer Colorectal Cancer Renal Cancer Melanoma	Drug: AZD2171 Radiation: Whole Brain Radiation	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Study of AZD2171 and WBRT in Patients With Brain Metastases

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Colorectal Cancer Kidney Cancer Lung Cancer Melanoma

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

To determine the safety and tolerability (maximum tolerated dose) of AZD2171 when combined with whole brain radiation therapy (WBRT) in patients with brain metastases. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To describe the objective response rate in the central nervous system, neurologic progression-free survival, overall survival and cause of death, and to explore the vascular normalization window using serial, non-invasive imaging parameters. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment:	3
Study Start Date:	September 2009
Estimated Study Completion Date:	July 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Taken orally once a day beginning 2 days prior to whole brain radiation therapy

14 consecutive weekdays, with weekends off

Other Name: WBRT

Detailed Description:

Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects, not everyone who participates in this research study will receive the same dose of the study drug. The dose will depend on the number of participants who have been enrolled in the study and how well the dose has been tolerated.
AZD2171 is taken orally once a day and participants will begin taking the study drug 2 days before the start of whole brain radiation.
For the first 3 weeks of the study, participants will be treated with radiation therapy to the whole brain. They will be receiving radiation therapy at the same time as they are taking study drug. When radiation is complete, they will continue to take the study drug daily without interruption.
Each 28 day period that participants take study drug is called a cycle of study treatment.
Participants will be required to monitor their blood pressure regularly. They will be given blood pressure monitoring equipment and be asked to record their blood pressure readings twice a day.
The following tests and procedures will be done within one week before the start of every 4-week cycle: Medical history; physical exam; vital signs; assessment of the tumor by MRI or CT; blood tests, EKG test and urine test.
As part of this study, participants will have special types of MRI studies called "Vascular MRIs". These are research MRIs designed to monitor the blood supply to the tumor and brain. The first Vascular MRI will be done between 1 and 5 days before participants begin treatment. An additional scan will be obtained 24 hours after the first dose of study drug but before the second dose. Vascular MRIs will also be done on days 21 and 49 of the study, and then once every other cycle going forward (every 56 days).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed non-small cell lung cancer, breast cancer, melanoma, colorectal cancer or renal cell cancer diagnosed no less than 12 weeks prior to study enrollment
Patients must have 1 or more radiologically proven parenchymal brain metastasis
No prior therapy for brain metastases
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
18 years of age or older
Karnofsky Performance Status of 70% or greater
Life expectancy of greater than 8 weeks
Normal organ and marrow function as outlined in the protocol
Mini-mental status exam (MMSE) score 15 or greater
Women of childbearing potential and men must agree so use adequate contraception prior to study entry and for the duration of study participation

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 earlier
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 epileptic drugs (NEIAE) or may be on no antiepileptic (AED) drugs. Patients off EIAED for 2 weeks or more are eligible.
Patients who have leptomeningeal disease as the only site of CNS involvement
Patients takin oral anticoagulant drugs
Patients with a mean corrected QT interval > 470 milliseconds (with Bazett'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
Patients with significant hemorrhage or hemoptysis
Patients who have brain imaging (CT or MRI) evidence of intra- or peri-tumoral hemorrhage
Patients who cannot undergo MRI safely
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, uncontrolled hypertension, NYHA 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 potential
Pregnant or nursing women
HIV-positive patients on combination antiretroviral therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00937482

Locations

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Massachusetts General Hospital

Dana-Farber Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

April F. Eichler, MD, MPH

Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	April Eichler, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00937482 History of Changes
Other Study ID Numbers:	09-089, 8213
Study First Received:	July 9, 2009
Last Updated:	May 4, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

AZD2171
WBRT
whole brain radiation

Additional relevant MeSH terms:

Breast Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Melanoma
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Adenocarcinoma
Carcinoma

Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Respiratory Tract Neoplasms

ClinicalTrials.gov processed this record on May 23, 2012