Clinical trial NCT00390806: Oral HYCAMTIN Plus Whole Brain Radiation Therapy In Treatment Of Brain Metastases Resulting From Non-Small Lung Cancer
Official title: A Randomized, Phase III, Open-Label Study of Oral Topotecan Plus Whole-Brain Radiation Therapy (WBRT) Compared With WBRT Alone in Patients With Brain Metastases From Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer, Non-Small Cell
Keywords: Brain metastases from Non-Small Cell Lung Cancer
Brain metastases brain tumor lung cancer oral chemotherapy HYCAMTIN topotecan NSCLC WBRT whole brain radiation
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-10-20
Enrollment: 472
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The current prognosis for patients with metastatic brain cancer from NSCLC is very poor. The current standard treatment for this disease is radiation therapy to the brain. The goal of the current study is to test whether the combination of orally administered HYCAMTIN capsules and whole brain radiation therapy will prolong the survival time of patients with this potentially serious condition.


Eligibility criteria: Inclusion criteria:

* At least one measurable cancerous lesion in the brain from primary non-small cell lung cancer (NSCLC)
* Must have received previous chemotherapy
* Must be 18 years of age of greater
* Must be Easter Cooperative Oncology Group (ECOG) Performance Status 0, 1, 2
* At least 2 weeks must have elapsed since any surgery
* At least 4 weeks must have elapsed since any radiation to a non-CNS site
* Must have adequate bone marrow, renal, and live capacities
* Women must be of non-childbearing potential or practice adequate birth control
* Males must practice adequate methods of birth control
* Must sign written informed consent

Exclusion criteria:

* Previous whole brain radiation therapy
* Prior treatment with topotecan
* Investigational agent within 30 days or 5 half-live
* Concomitant therapy with inhibitors of breast cancer resistance protein (BCRP) or P-glycoprotein such as erlotinib or gefitinib
* Primary or secondary immunodeficiencies
* Gastrointestinal conditions that affect GI absorption or motility
* Uncontrolled emesis
* Brain metastasis at time of initial diagnosis of NSCLC
* History of other malignancy except in situ carcinoma of cervix; nonmelanomatous skin cancer, low grade prostate cancer
* Pregnant or intending to become pregnant or intending to father a baby
* Any severe concurrent medical condition that could affect compliance.

Primary outcomes:
measure: Overall Survival
timeFrame: From the time of Randomization until the date of death due to any cause (up to 195 weeks)
Secondary outcomes:
measure: Six-month Survival
timeFrame: Month 6
measure: Number of Participants With a Complete Response (CR) or a Partial Response (PR) (Central Nervous System [CNS]-Radiologic)
timeFrame: From the time of Randomization until the time of CR or PR (up to 75 weeks)
measure: Time to Response (TTR) (CNS-radiologic)
timeFrame: From the time of Randomization until the first documented evidence of CR or PR (up to 75 weeks)
measure: Time to Progression (TTP) (CNS-radiologic)
timeFrame: From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)
measure: Time to Progression (TTP) (All Sites of Disease-radiologic)
timeFrame: From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)
measure: Number of Participants Who Ranked Each Individual Indicated Neurological Sign and Symptom as None, Mild, Moderate, or Severe at Months 1 and 3
timeFrame: Months 1 and 3
measure: Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Level of Consciousness at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Headache at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Dizziness/Lightheadedness at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Vertigo at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Nausea/Vomiting at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Visual Problem at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Seizure at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Other Neurological Symptoms at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Cranial Nerves II-XII at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Language (Dysphasia or Aphasia) at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Strength (Right Upper Extremity) at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Strength (Left Upper Extremity) at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Strength (Right Lower Extremity) at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Strength (Left Lower Extremity) at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Sensation at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Ataxia (Right Upper Extremity: Finger to Nose Testing) at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Ataxia (Left Upper Extremity: Finger to Nose Testing) at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Ataxia (Gait) at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With the Indicated Investigator Assessment of Ataxia (Balance) at Baseline, Month 1, and Month 3
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants With Any Adverse Event (AE; Both Serious and Non-serious) or Serious Adverse Event (SAE)
timeFrame: From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)
measure: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Chemistry Parameters With Respect to the Normal Range
timeFrame: From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)
measure: Lesion Assessment and Measurement
timeFrame: From the time of Randomization until the time of CR or PR (up to 75 weeks)
measure: Brain Symptoms
timeFrame: Baseline, Month 1, and Month 3
measure: Number of Participants Who Died or Progressed
timeFrame: From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Glendale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Hot Springs
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Duarte
country: United States
facility: GSK Investigational Site
state: California
city: Pleasant Hill
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: Lakeland
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Elk Grove Village
country: United States
facility: GSK Investigational Site
state: Illinois
city: Galesburg
country: United States
facility: GSK Investigational Site
state: Illinois
city: Park Ridge
country: United States
facility: GSK Investigational Site
state: Illinois
city: Rockford
country: United States
facility: GSK Investigational Site
state: Illinois
city: Skokie
country: United States
facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Westwood
country: United States
facility: GSK Investigational Site
state: Kansas
city: Paducah
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Jackson
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Columbia
country: United States
facility: GSK Investigational Site
state: Missouri
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Lincoln
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Bronx
country: United States
facility: GSK Investigational Site
state: New York
city: Buffalo
country: United States
facility: GSK Investigational Site
state: New York
city: Buffalo
country: United States
facility: GSK Investigational Site
state: New York
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Eugene
country: United States
facility: GSK Investigational Site
state: Oregon
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Bedford
country: United States
facility: GSK Investigational Site
state: Texas
city: Corpus Christi
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Duncanville
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Lubbock
country: United States
facility: GSK Investigational Site
state: Texas
city: Sherman
country: United States
facility: GSK Investigational Site
state: Texas
city: Sugarland
country: United States
facility: GSK Investigational Site
state: Texas
city: Everett
country: United States
facility: GSK Investigational Site
state: Washington
city: Vancouver
country: United States
facility: GSK Investigational Site
state: Washington
city: Madison
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Moncton
country: Canada
facility: GSK Investigational Site
state: New Brunswick
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Kingston
country: Canada
facility: GSK Investigational Site
state: Ontario
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Greenfield Park
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Csorna
country: Hungary
facility: GSK Investigational Site
city: Gyula
country: Hungary
facility: GSK Investigational Site
city: Győr
country: Hungary
facility: GSK Investigational Site
city: Miskolc
country: Hungary
facility: GSK Investigational Site
city: Mátraháza
country: Hungary
facility: GSK Investigational Site
city: Nyíregyháza
country: Hungary
facility: GSK Investigational Site
city: Pécs
country: Hungary
facility: GSK Investigational Site
city: Szombathely
country: Hungary
facility: GSK Investigational Site
city: Székesfehérvár
country: Hungary
facility: GSK Investigational Site
city: Törökbálint
country: Hungary
facility: GSK Investigational Site
city: Zalaegerszeg-Pozva
country: Hungary
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Kazan
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Obninsk
country: Russian Federation
facility: GSK Investigational Site
city: Orenburg
country: Russian Federation
facility: GSK Investigational Site
city: St-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Voronezh
country: Russian Federation
facility: GSK Investigational Site
city: Banska Bystrica
country: Slovakia
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Nitra
country: Slovakia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: