Single-agent Erlotinib in Patients Previously Treated With Oral Etoposide in Protocol OSI-774-205

Open-label Phase 2 Study of Single-agent Erlotinib for Patients With Pediatric Ependymoma Previously Treated With Oral Etoposide in Protocol OSI-774-205

Participants that were assigned to the oral etoposide treatment arm in protocol OSI-774-205 and either progressed while on study or discontinued due to unacceptable toxicity related to etoposide were allowed to participate in this study to assess the safety profile of single-agent erlotinib in participants with recurrent or refractory pediatric ependymoma.

Study Overview

• Status: Terminated
• Conditions: Ependymoma
• Intervention / Treatment: Drug: Erlotinib

Detailed Description

The protocol-specified futility criteria were met at the second interim analysis dated 15 Aug 2012 for OSI-774-205. Per the Data Monitoring Committee's recommendation and FDA's agreement, the enrollment of patients in that study and Study OSI-774-206 was permanently closed.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Stollery Children's Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's and Women's Health Center of BC
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital Oncology Department
  • Glasgow, United Kingdom, G3 8SJ
    • Royal Hospital for Sick Children
  • Leeds, United Kingdom, LS1 3EX
    • Paediatric Oncology and Haematology Offices,
  • Liverpool, United Kingdom, L12 1AP
    • Alder Hey Children's NHS Foundation Trust
  • Manchester, United Kingdom, M13 9W2
    • Royal Manchester Children's Hospital Ward 84
  • Nottingham, United Kingdom, NG7 2UH
    • University of Nottingham
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County (CHOC)
    • Palo Alto, California, United States, 94304
      • Packard Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital Center for Cancer and Blood Disorders
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center -D.C. Center for Cancer and Blood Disorders
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Children's Healthcare of Atlanta
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota - Amplatz Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97124
      • Oregon Health & Sciences University Doernbecher Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Childrens Hospital Of Pittsburgh Of Upmc
  • Wisconsin
    • Madison, Wisconsin, United States, 53705-2275
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have been enrolled in OSI-774-205, been randomized to oral etoposide and either progressed while on study or discontinued due to unacceptable toxicity related to etoposide
• Performance status: Lansky ≥ 50% for patients ≤ 10 years of age or younger or Karnofsky ≥ 50% for patients greater than 10 years of age
• Patients must have recovered from any acute toxicity to any prior anti-cancer treatment
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, serum glutamic pyruvic transaminase (SGPT) ALT ≤ 3 x ULN
• Serum creatinine based on age OR Creatinine Clearance/Glomerular Filtration Rate (GFR) ≥ 70 mL/min/m2
• Patients must be neurologically stable for at least 7 days before registration
• Patients, both males and females, with reproductive potential must agree to practice effective contraceptive measures for the duration of study drug therapy and for at least 90 days after completion of study drug therapy
• Patients must be able to take erlotinib orally

Exclusion Criteria:

• Taking strong/moderate CYP3A4 or CYP1A2 inhibitors/inducers ≤ 14 days before registration
• Have received any other chemotherapy or immunotherapy to treat ependymoma after discontinuation from OSI-774-205
• Taking proton pump inhibitors ≤ 14 days before registration
• Participating in another investigational drug trial while on study
• Pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib; Participants who received erlotinib in a continuous oral dose of 85 mg/m^2 per day until dose modification, interruption or study discontinuation occurred.	Drug: Erlotinib; continuous oral Erlotinib 85 mg/m^2 per day; Other Names: Tarceva; OSI-774

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessed Through Evaluation of Physical Examinations, Vital Signs, Clinical Laboratory Tests, and Adverse Events (AEs)	Safety is monitored through AEs, which includes abnormal or clinically significant vital sign assessments, laboratory test, physical examination findings associated with signs and/or symptoms requiring withdrawal, dose modification or medical intervention. A treatment-emergent adverse event (TEAE) was defined as an adverse event observed after starting administration of the study drug. An AE was considered serious (SAE) 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.	From first dose of study drug to 30 days after last dose of study drug (The mean treatment duration was 170.5 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response	Best overall response was derived from an integrated clinical assessment by the study investigator as per institutional standards. This included radiographic assessments deemed appropriate by the investigator in the normal care of the patient. A determination of best overall response at the end of study treatment (complete response, partial response, minor response or stable disease) was only made if (1) any disease-related neurologic symptoms were stable or improving over the interval of the radiographic assessment and (2) corticosteroid dosing for the control of tumor-related signs/symptoms was stable or decreasing.If the investigator deems that a radiographic assessment is not needed, then evidence of clinical improvement may be used to determine best response provided that corticosteroid dosing for tumor-related signs/symptoms is stable or decreasing.	End of treatment (The mean treatment duration was 170.5 days.)
Median Treatment Duration		From first dose of study drug up to last dose of study drug (The mean treatment duration was 170.5 days)

Collaborators and Investigators

• Sponsor: OSI Pharmaceuticals
• Investigators: Study Director: Medical Monitor, Astellas Pharma Global Development

Publications and helpful links

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2011
• Primary Completion (Actual): September 13, 2012
• Study Completion (Actual): September 13, 2012

Study Registration Dates

• First Submitted: November 23, 2010
• First Submitted That Met QC Criteria: November 24, 2010
• First Posted (Estimated): November 25, 2010

Study Record Updates

• Last Update Posted (Actual): December 6, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Erlotinib; Ependymoma; Tarceva; Pediatric Ependymoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Ependymoma; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: OSI-774-206; 2010-023478-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.