Recurrent or Refractory Pediatric Ependymoma
Conditions
Keywords
pediatric, etoposide, erlotinib, phase 2, ependymoma
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.
Interventions
DRUGerlotinib
oral
DRUGetoposide
oral
Sponsors
OSI Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Objective Response | From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. | 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
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. | 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 | From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. | 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 | From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. | 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) | From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. | 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 | From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. | 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 | From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide. | 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) | 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. | 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) | 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. | 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 | Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. | 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) | Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. | 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) | Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. | 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 | Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. | 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 | Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose. | 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. |
Countries
Canada, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 13 |
| 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. | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease progression | 13 | 8 |
| Overall Study | Medical or ethical reasons | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Erlotinib | Etoposide | Total |
|---|---|---|---|
| Age, Continuous | 12.8 years STANDARD_DEVIATION 5.87 | 9.2 years STANDARD_DEVIATION 4.99 | 11.1 years STANDARD_DEVIATION 5.67 |
| Body Surface Area (BSA) | 1.51 m^2 STANDARD_DEVIATION 0.556 | 1.17 m^2 STANDARD_DEVIATION 0.439 | 1.35 m^2 STANDARD_DEVIATION 0.521 |
| Race/Ethnicity, Customized Asian - Indian Subcontinent | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian - Southeast Asia | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 12 participants | 10 participants | 22 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 11 participants | 9 participants | 20 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 19 Participants |
| Total Number of Disease Recurrences | 3 recurrences FULL_RANGE 2.1 | 2 recurrences FULL_RANGE 0.8 | 2 recurrences FULL_RANGE 1.7 |
| Tumor Type for Initial Disease Diagnosis Anaplastic Ependymoma | 6 participants | 9 participants | 15 participants |
| Tumor Type for Initial Disease Diagnosis Ependymoma | 6 participants | 3 participants | 9 participants |
| Tumor Type for Initial Disease Diagnosis Myxopapillary Ependymoma | 1 participants | 0 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 11 / 12 |
| serious Total, serious adverse events | 6 / 13 | 5 / 12 |
Outcome results
Primary
Percentage of Participants With an Objective Response
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.
Time frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
Population: The Full Analysis Set (FAS) consisted of all randomized participants. Following the intent-to-treat (ITT) principle, participants were analyzed according to the treatment arm they were assigned to at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With an Objective Response | 0 percentage of participants |
| Etoposide | Percentage of Participants With an Objective Response | 16.7 percentage of participants |
Comparison: The study was not powered for this comparison due to small sample size.p-value: 0.22Fisher Exact
Secondary
Apparent Body Clearance (CL/F) of Erlotinib
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.
Time frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
Population: The Pharmacokinetics Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Erlotinib | Apparent Body Clearance (CL/F) of Erlotinib | 2922.1 mL/h/m^2 |
Secondary
Apparent Volume of Distribution (Vz/F) of Erlotinib
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.
Time frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
Population: The Pharmacokinetics Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Erlotinib | Apparent Volume of Distribution (Vz/F) of Erlotinib | 71628.5 mL/m^2 |
Secondary
Area Under the Curve From Time 0 to 24 Hours Post-dose for Erlotinib
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.
Time frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
Population: The Pharmacokinetics Analysis Set (PKAS) consisted of the participants treated with erlotinib for whom sufficient analyte concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter. Participants may have been excluded from the PKAS for reasons such as missing data or protocol deviation.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Erlotinib | Area Under the Curve From Time 0 to 24 Hours Post-dose for Erlotinib | 26716.7 h*ng/mL |
Secondary
Duration of Response
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.
Time frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
Population: Full Analysis Set participants whose best overall response was CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Etoposide | Duration of Response | NA days |
Secondary
Duration of Stable Disease
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.
Time frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
Population: Full Analysis Set participants whose best overall response was CR, PR, MR or SD.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Duration of Stable Disease | 79 days |
| Etoposide | Duration of Stable Disease | NA days |
Secondary
Maximum Observed Plasma Concentration of Erlotinib (Cmax)
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 frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
Population: The Pharmacokinetics Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Erlotinib | Maximum Observed Plasma Concentration of Erlotinib (Cmax) | 1969.5 ng/mL |
Secondary
Overall Survival (OS)
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.
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.
Population: The Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Overall Survival (OS) | NA days |
| Etoposide | Overall Survival (OS) | 261 days |
Secondary
Percentage of Participants With a Minor Response
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.
Time frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
Population: The Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With a Minor Response | 0 percentage of participants |
| Etoposide | Percentage of Participants With a Minor Response | 25.0 percentage of participants |
Secondary
Percentage of Participants With Disease Control
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.
Time frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
Population: The Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With Disease Control | 15.4 percentage of participants |
| Etoposide | Percentage of Participants With Disease Control | 41.7 percentage of participants |
Secondary
Percentage of Participants With Prolonged Stable Disease
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.
Time frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
Population: The Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Percentage of Participants With Prolonged Stable Disease | 0 percentage of participants |
| Etoposide | Percentage of Participants With Prolonged Stable Disease | 41.7 percentage of participants |
Secondary
Progression Free Survival (PFS)
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.
Time frame: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
Population: The Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib | Progression Free Survival (PFS) | 52 days |
| Etoposide | Progression Free Survival (PFS) | 65 days |
Secondary
Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs)
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.
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.
Population: All enrolled participants who received at least 1 dose of study drug (Safety Analysis Set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Any adverse event | 13 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related adverse event | 11 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Adverse event leading to death | 1 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related adverse event leading to death | 0 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Serious adverse event | 6 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related serious adverse event | 0 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | AE leading to discontinuation | 0 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related AE leading to discontinuation | 0 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | AE leading to dose interruption | 2 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related AE leading to dose interruption | 1 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | AE leading to dose interruption and reduction | 1 participants |
| Erlotinib | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Related AE leading to dose interruption/ reduction | 1 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | AE leading to dose interruption and reduction | 2 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Any adverse event | 11 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | AE leading to discontinuation | 0 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related adverse event | 10 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related AE leading to dose interruption | 3 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Adverse event leading to death | 0 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related AE leading to discontinuation | 0 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related adverse event leading to death | 0 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Related AE leading to dose interruption/ reduction | 2 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Serious adverse event | 5 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | AE leading to dose interruption | 5 participants |
| Etoposide | Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs) | Drug-related serious adverse event | 1 participants |
Secondary
Time to Maximum Observed Plasma Concentration of Erlotinib (Tmax)
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.
Time frame: Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.
Population: The Pharmacokinetics Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Erlotinib | Time to Maximum Observed Plasma Concentration of Erlotinib (Tmax) | 2.100 hours |