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

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00937482
First received: July 9, 2009
Last updated: March 7, 2013
Last verified: March 2013
  Purpose

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


Condition Intervention Phase
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
Drug: cediranib maleate
Radiation: whole-brain radiation therapy
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 1 Study of AZD2171 and WBRT in Patients With Brain Metastases

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: 7 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective response in the CNS [ Time Frame: Up to 1.5 years ] [ Designated as safety issue: No ]
  • Neurologic progression-free survival [ Time Frame: Time from start of treatment to time of progression in the CNS, assessed up to 1.5 years ] [ Designated as safety issue: No ]
    N-PFS will be summarized using a Kaplan-Meier survival curve.

  • Overall survival [ Time Frame: From study entry until death due to any cause, assessed up to 1.5 years ] [ Designated as safety issue: No ]
    Overall survival will be summarized using a Kaplan-Meier survival curve.

  • Cause of death [ Time Frame: Up to 1.5 years ] [ Designated as safety issue: No ]
    The proportion of patients who fall into each category will be tabulated.

  • Vascular MRI studies [ Time Frame: Up to 1.5 years ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: August 2009
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cediranib maleate and WBRT)
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
Given orally
Other Names:
  • AZD2171
  • Recentin
Radiation: whole-brain radiation therapy
Undergo whole-brain radiotherapy
Other Names:
  • WBRT
  • whole-brain radiotherapy

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

  Eligibility

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

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 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
  • HIV-positive patients on combination antiretroviral therapy are ineligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Investigators
Principal Investigator: April Eichler Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00937482     History of Changes
Other Study ID Numbers: NCI-2013-00575, 09-089, U01CA062490
Study First Received: July 9, 2009
Last Updated: March 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Breast Neoplasms
Rectal Neoplasms
Colonic Neoplasms
Carcinoma, Renal Cell
Breast Neoplasms, Male
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Breast Diseases
Skin Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on September 18, 2014