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Erlotinib Versus Oral Etoposide in Patients With Recurrent or Refractory Pediatric Ependymoma (PETEY)

This study has been terminated.
(In a pre-planned interim analysis, OSI-774-205 met futility for efficacy with no safety concerns. As a result, it has been stopped.)
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( OSI Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01032070
First received: December 10, 2009
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Recurrent or Refractory Pediatric Ependymoma
Drug: erlotinib
Drug: etoposide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Phase 2 Study of Single-agent Erlotinib Versus Oral Etoposide in Patients With Recurrent or Refractory Pediatric Ependymoma

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Percentage of Participants With an Objective Response [ Time Frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. ] [ Designated as safety issue: No ]

    Objective response is defined as a best overall response of complete response (CR) or partial response (PR), evaluated using modified International Society of Pediatric Oncology Brain, Tumor Subcommittee for the Reporting of Trials criteria. Response was confirmed at least 28 days after the first assessment where the response criteria were met. Response was assessed by magnetic resonance imaging (MRI) every 8 weeks.

    CR:

    • Complete disappearance of all enhancing tumor and mass effect
    • On a stable or decreasing dose of corticosteroids (or receiving only adrenal replacement doses)
    • Stable or improving neurologic examination sustained for ≥ 4 weeks
    • If cerebral spinal fluid (CSF) evaluation was positive, it must become negative (confirmed at least 2 times at consecutive samplings).

    PR:

    • ≥ 50% reduction in tumor size by bi-dimensional measurement
    • On a stable or decreasing dose of corticosteroids
    • Stable or improving neurologic examination sustained for ≥ 4 weeks.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. ] [ Designated as safety issue: No ]

    Duration of response (complete or partial response [CR/PR]) was defined as the time from the date of the first documented response (CR/PR) to the first documented progression or death due to underlying cancer. If a participant had not progressed or died, the duration of overall response was censored at the date of last adequate disease assessment. Duration of response was only defined for participants whose best overall response was CR or PR.

    Progression was defined as a worsening of neurologic status that could not be explained by other causes, a > 25% increase in tumor size, the appearance of new lesions or CSF positivity, or increasing doses of corticosteroids required to maintain stable status.


  • Percentage of Participants With a Minor Response [ Time Frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. ] [ Designated as safety issue: No ]

    Participants with a best overall response of minor response (MR), defined as:

    • ≥ 25% to < 50% reduction in tumor size by bi-dimensional measurement
    • On a stable or decreasing dose of corticosteroids
    • Stable or improving neurologic examination sustained for ≥ 4 weeks.

  • Percentage of Participants With Disease Control [ Time Frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. ] [ Designated as safety issue: No ]

    Disease control is a best overall response of CR or PR or MR or Stable disease (SD).

    CR:

    • Complete disappearance of all enhancing tumor and mass effect
    • On a stable or decreasing dose of corticosteroids
    • Stable or improving neurologic examination sustained for ≥ 4 weeks
    • If CSF evaluation was positive, it must become negative (confirmed at least 2 times consecutively).

    PR:

    • ≥ 50% reduction in tumor size by bi-dimensional measurement
    • On a stable or decreasing dose of corticosteroids
    • Stable or improving neurologic examination sustained for ≥ 4 weeks.

    MR:

    • ≥ 25% to < 50% reduction in tumor size by bi-dimensional measurement
    • On a stable or decreasing dose of corticosteroids
    • Stable or improving neurologic examination sustained for ≥ 4 weeks.

    SD:

    • Neurologic examination is at least stable
    • Maintenance corticosteroid dose is not increased
    • MRI meets neither the criteria for minor response nor for progressive disease
    • Sustained for ≥ 8 weeks.

  • Progression Free Survival (PFS) [ Time Frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. ] [ Designated as safety issue: No ]

    Progression-free survival was defined as the time from randomization to disease progression based on central nervous system (CNS)-specific evaluation criteria as assessed by the investigator or death due to any cause, whichever occurs first.

    Participants did not progress or die before the data cutoff date for analysis were censored at the date of last disease assessment (including both radiologic assessment and neurologic assessment) where non-progression was documented. If a participant received any further anticancer therapy without prior documentation of disease progression, the participant was censored at the date of last disease assessment before starting new anti-cancer treatment. Participants were also censored at the date of last disease assessment with no documented progression if patients discontinued treatment for undocumented progression, toxicity or other reason before the data cutoff date for analysis.


  • Percentage of Participants With Prolonged Stable Disease [ Time Frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. ] [ Designated as safety issue: No ]
    Prolonged stable disease (SD) was defined as SD with a duration of at least 16 weeks. The percentage of participants with prolonged SD was defined as participants who achieved a best overall response of CR or PR or MR or SD, and did not progress within 16 weeks from randomization. Progression was defined as a worsening of neurologic status that could not be explained by other causes, a > 25% increase in tumor size, the appearance of new lesions or CSF positivity, or increasing doses of corticosteroids required to maintain stable status.

  • Duration of Stable Disease [ Time Frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. ] [ Designated as safety issue: No ]

    Duration of stable disease (SD; defined as participants with an overall best response of complete, partial or minor response or stable disease) was defined as the time from the date of randomization to the first documented progression or death due to underlying cancer. If a participant had not progressed or died, the duration of SD was censored at the date of last adequate disease assessment. Duration of SD was only defined for participants whose best overall response was CR or PR or MR or SD.

    Progression was defined as a worsening of neurologic status that could not be explained by other causes, a > 25% increase in tumor size, the appearance of new lesions or CSF positivity, or increasing doses of corticosteroids required to maintain stable status.


  • Overall Survival (OS) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the date of randomization until the documented date of death. Participants who were still alive by the data cutoff date for analysis were censored on the last day the participant was known to be alive.

  • Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) [ Time Frame: 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. ] [ Designated as safety issue: No ]

    An AE was defined as any untoward medical occurrence in a study participant and did not necessarily have a causal relationship with study treatment. Clinically significant vital sign assessments, findings on physical or neurological examination, and laboratory findings associated with signs and/or symptoms requiring withdrawal, dose modification or medical intervention were recorded as AEs.

    An AE was considered serious if it resulted in death, a life-threatening situation, inpatient hospitalization or prolongation of an existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a patient who received study drug or other important medical events. The relationship of each AE to study drug was assessed as either related or not related.


  • Area Under the Curve From Time 0 to 24 Hours Post-dose for Erlotinib [ Time Frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. Area under the plasma concentration-time curve from time zero to 24 hours (the dosing interval) measured at steady state using sparse sampling.

  • Maximum Observed Plasma Concentration of Erlotinib (Cmax) [ Time Frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. Maximum observed plasma concentration of erlotinib (Cmax) was measured at steady state on Day 14 using sparse sampling.

  • Time to Maximum Observed Plasma Concentration of Erlotinib (Tmax) [ Time Frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. Time to the maximum observed plasma concentration of erlotinib (Tmax) was measured at steady state on Day 14 using sparse sampling.

  • Apparent Body Clearance (CL/F) of Erlotinib [ Time Frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. Apparent body clearance (CL/F) of erlotinib was measured at steady state on Day 14 using sparse sampling.

  • Apparent Volume of Distribution (Vz/F) of Erlotinib [ Time Frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters were determined from the serial plasma concentration data obtained for erlotinib. The apparent volume of distribution (Vz/F) of erlotinib was measured at steady state on Day 14 using sparse sampling.


Enrollment: 25
Study Start Date: September 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib
Erlotinib was administered orally at a dose of 85 mg/m^2 per day continuously until either progression, death, patient request or investigator decision to discontinue study drug or intolerable toxicity.
Drug: erlotinib
oral
Other Names:
  • Tarceva
  • OSI-774
Active Comparator: Etoposide
Etoposide 50 mg/m^2 per day was administered orally for 21 days followed by a 7-day rest period until either progression, death, patient request or investigator decision to discontinue study drug or intolerable toxicity.
Drug: etoposide
oral
Other Name: VP-16

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

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01032070

  Show 28 Study Locations
Sponsors and Collaborators
OSI Pharmaceuticals
Investigators
Study Director: Medical Monitor Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( OSI Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01032070     History of Changes
Other Study ID Numbers: OSI-774-205, 2009-016836-11
Study First Received: December 10, 2009
Results First Received: November 20, 2013
Last Updated: November 20, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
phase 2
erlotinib
pediatric
etoposide
ependymoma

Additional relevant MeSH terms:
Ependymoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Erlotinib
Etoposide
Etoposide phosphate
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014