Cediranib Maleate and Whole Brain Radiation Therapy in Patients With Brain Metastases From Non-Small Cell Lung Cancer

NCT00937482 | Terminated Phase 1

• 3 other identifiers: NCI-2013-0057509-089U01CA062490
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of cediranib maleate when given together with whole brain radiation therapy in treating patients with brain metastases from non-small cell lung cancer. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays and other types of radiation to kill cancer cells and shrink tumors. Giving cediranib maleate together with radiation therapy may kill more tumor cells

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  7 weeks

Secondary Outcomes (5)

• Objective response in the CNS

  Up to 1.5 years

• Neurologic progression-free survival

  Time from start of treatment to time of progression in the CNS, assessed up to 1.5 years

• Overall survival

  From study entry until death due to any cause, assessed up to 1.5 years

• Cause of death

  Up to 1.5 years

• Vascular MRI studies

  Up to 1.5 years

Study Arms (1)

Treatment (cediranib maleate and WBRT)

EXPERIMENTAL

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.

Drug: cediranib maleate; Radiation: whole-brain radiation therapy

Interventions

cediranib maleate DRUG

Given orally

Also known as: AZD2171, Recentin

Treatment (cediranib maleate and WBRT)

whole-brain radiation therapy RADIATION

Undergo whole-brain radiotherapy

Also known as: WBRT, whole-brain radiotherapy

Treatment (cediranib maleate and WBRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms; Melanoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Colonic Neoplasms; Rectal Neoplasms; Brain Neoplasms

Interventions

cediranib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• April Eichler

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 13, 2009
• Study Start: August 1, 2009
• Primary Completion: March 1, 2011
• Last Updated: March 8, 2013

Record last verified: 2013-03

Locations

US (1)