Clinical trial NCT01032070: Erlotinib Versus Oral Etoposide in Patients With Recurrent or Refractory Pediatric Ependymoma
Official title: A Randomized, Phase 2 Study of Single-agent Erlotinib Versus Oral Etoposide in Patients With Recurrent or Refractory Pediatric Ependymoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent or Refractory Pediatric Ependymoma
Keywords: pediatric
etoposide
erlotinib
phase 2
ependymoma
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2009-12-15
Enrollment: 25
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 2 study to evaluate the efficacy of single-agent erlotinib versus oral etoposide in patients with recurrent or refractory pediatric ependymoma.

Detailed description: This is a phase 2 study involving a 1:1 randomization of 40 patients with recurrent or refractory pediatric ependymoma who will receive either erlotinib or oral etoposide.

Eligibility criteria: Inclusion Criteria:

* Recurrent of refractory ependymoma or subependymoma
* Performance Status (PS): Lansky ≥ 50% for patients ≤ 10 years of age or Karnofsky ≥ 50% for patients \>10 years of age
* Measurable disease, defined as 1 measurable lesion that can be accurately measured in 2 planes that has not received radiation therapy within 12 weeks
* Recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
* ≥ 1 year to ≤ 21 years
* Serum creatinine for patients ≤ 5 years in age is ≤ 0.8 mg/dL or Creatinine Clearance/Glomerular Filtration Rate (GFR) ≥ 70 mL/min/m\^2
* Serum creatinine for patients \> 5 and ≤ 10 years in age is ≤ 1.0 mg/dL or Creatinine Clearance/GFR ≥ 70 mL/min/m\^2
* Serum creatinine for patients \> 10 and ≤ 15 years in age is ≤ 1.2 mg/dL or Creatinine Clearance/GFR ≥ 70 mL/min/m\^2
* Serum creatinine for patients \> 15 years in age is ≤ 1.5 mg/dL or Creatinine Clearance/GFR ≥ 70 mL/min/m\^2
* Total bilirubin is ≤ 1.5 x upper limit of normal for age
* Alanine aminotransferase (ALT) ≤ 3 x upper limit of normal
* Absolute neutrophil count \> 1000/µL
* Platelet count \> 100,000/µL
* Hemoglobin \> 8 gm/dL
* Neurologically stable for at least 7 days prior to randomization
* If receiving corticosteroids, patients must be on a stable or decreasing dose for at least 7 days before randomization
* Patients of reproductive potential must agree to proactive effective contraceptive measures for the duration of the study and for at least 90 days after completion of study drug

Exclusion Criteria:

* Previously received epidermal growth factor receptor (EGFR)-targeted therapy
* Previously received oral etoposide
* Received craniospinal radiotherapy within 24 weeks prior to randomization
* Received field radiotherapy to the target lesion within 12 weeks prior to randomization
* Received symptomatic metastatic disease within 14 days prior to randomization
* Received myelosuppressive chemotherapy within 21 days before randomization
* Received growth factors within 7 days prior to randomization
* Participating in another investigational drug trial
* Received a biologic agent within 7 days prior to randomization
* Received a monoclonal antibody within 28 days prior to randomization
* Taking cytochrome P450 (CYP)3A4 or CYP1A2 inhibitors/inducers within 14 days prior to randomization
* Taking proton pump inhibitors within 14 days prior to randomization
* Smoking during treatment
* Pregnant or breast-feeding females

Primary outcomes:
measure: Percentage of Participants With an Objective Response
timeFrame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
Secondary outcomes:
measure: Duration of Response
timeFrame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
measure: Percentage of Participants With a Minor Response
timeFrame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
measure: Percentage of Participants With Disease Control
timeFrame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
measure: Progression Free Survival (PFS)
timeFrame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
measure: Percentage of Participants With Prolonged Stable Disease
timeFrame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
measure: Duration of Stable Disease
timeFrame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
measure: Overall Survival (OS)
timeFrame: From randomization up to 12 months after the last dose. Median duration of follow-up was 12.9 months for erlotinib and 14.4 months for etoposide.
measure: Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs)
timeFrame: From the date of first dose of study drug until 30 days after the last dose. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
measure: Area Under the Curve From Time 0 to 24 Hours Post-dose for Erlotinib
timeFrame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
measure: Maximum Observed Plasma Concentration of Erlotinib (Cmax)
timeFrame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
measure: Time to Maximum Observed Plasma Concentration of Erlotinib (Tmax)
timeFrame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
measure: Apparent Body Clearance (CL/F) of Erlotinib
timeFrame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
measure: Apparent Volume of Distribution (Vz/F) of Erlotinib
timeFrame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Dept. of Pediatric-Hematology/Oncology
state: Alabama
city: Phoenix
country: United States
facility: Center for Cancer and Blood Disorders-Phoenix Children's Hospital
state: Arizona
city: Orange
country: United States
facility: Children's Hospital of Orange County (CHOC)
state: California
city: Palo Alto
country: United States
facility: Stanford University and Lucile Packard Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Center for Cancer and Blood Disorders
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center - D.C. Center for Cancer and Blood Disorders
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University Children's Healthcare of Atlanta Aflac Cancer Center & Blood Disorders
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute Department of Pediatric Neuro-oncology
state: Massachusetts
city: Minneapolis
country: United States
facility: Amplatz Children's Hospital University of Minnesota Medical Center- Pediatric Hematology Oncology
state: Minnesota
city: New York
country: United States
facility: Steven D Hassenfeld Children's Center - New York University
state: New York
city: New York
country: United States
facility: Columbia University Children's Hospital of New York Presbyterian Child & Adolescent Oncology Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Sciences University Doembecher Children's Hospital
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Children's Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center, Dallas Center for Cancer and Blood Disorders
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Pediatric Hematology/Oncology Department
state: Wisconsin
city: Edmonton
country: Canada
facility: Strollery Children's Hospital Division of Hematology/Oncology
state: Alberta
city: Vancouver
country: Canada
facility: Children's and Women's Health Center of BC Division of Hematology/ Oncology/ BMT
state: British Columbia
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
city: Leeds
country: United Kingdom
facility: Paediatric Oncology and Haematology Offices
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust Department of Oncology
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital Ward 84
city: Nottingham
country: United Kingdom
facility: University of Nottingham Children's Brain Tumour Research Centre
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Monitor
role: STUDY_DIRECTOR
References: