Ependymoma
Conditions
Keywords
Pediatric Ependymoma, Ependymoma, Tarceva, Erlotinib
Brief summary
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.
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.
Interventions
DRUGErlotinib
continuous oral Erlotinib 85 mg/m\^2 per day
Sponsors
OSI Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Assessed Through Evaluation of Physical Examinations, Vital Signs, Clinical Laboratory Tests, and Adverse Events (AEs) | From first dose of study drug to 30 days after last dose of study drug (The mean treatment duration was 170.5 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | End of treatment (The mean treatment duration was 170.5 days.) | 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. |
| Median Treatment Duration | From first dose of study drug up to last dose of study drug (The mean treatment duration was 170.5 days) | — |
Countries
Canada, United Kingdom, United States
Participant flow
Recruitment details
Participants recruited for this OSI-774-206 study were participants with pediatric ependymoma previously treated with oral etoposide in Study OSI-774-205 who progressed while on study or discontinued due to unacceptable toxicity.
Pre-assignment details
Participants who consented to enter this OSI-774-206 study and fulfilled all the eligibility criteria (no more than 14 days prior to registration) were enrolled in this study no more than 21 days from the last dose of oral etoposide in Study OSI-774-205.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 4 |
Baseline characteristics
| Characteristic | Erlotinib |
|---|---|
| Age, Categorical <=18 years | 4 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Race/Ethnicity, Customized Asian-Indian subcontinent | 1 participants |
| Race/Ethnicity, Customized White | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
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.
Time frame: From first dose of study drug to 30 days after last dose of study drug (The mean treatment duration was 170.5 days)
Population: The analysis population is the Safety Analysis Set (SAF) consisted of all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Safety Assessed Through Evaluation of Physical Examinations, Vital Signs, Clinical Laboratory Tests, and Adverse Events (AEs) | Any TEAE | 4 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Examinations, Vital Signs, Clinical Laboratory Tests, and Adverse Events (AEs) | With at least 1 SAE | 2 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Examinations, Vital Signs, Clinical Laboratory Tests, and Adverse Events (AEs) | With at least 1 treatment-related SAE | 0 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Examinations, Vital Signs, Clinical Laboratory Tests, and Adverse Events (AEs) | Discontinued study due to treatment-related AEs | 0 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Examinations, Vital Signs, Clinical Laboratory Tests, and Adverse Events (AEs) | Died on treatment or within 30 days | 1 participants |
Secondary
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.
Time frame: End of treatment (The mean treatment duration was 170.5 days.)
Population: SAF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Best Overall Response | Complete response | 0 participants |
| Erlotinib | Best Overall Response | Partial response | 0 participants |
| Erlotinib | Best Overall Response | Minor response | 0 participants |
| Erlotinib | Best Overall Response | Stable disease | 2 participants |
| Erlotinib | Best Overall Response | Disease progression | 2 participants |
Secondary
Median Treatment Duration
Time frame: From first dose of study drug up to last dose of study drug (The mean treatment duration was 170.5 days)
Population: SAF
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Median Treatment Duration | 91.0 days |