OSI-774-205

OSI Pharmaceuticals LLC

1 Astellas Way, Northbrook, United States,

Clinical Trial Disclosure, Astellas Pharma Global Devlopment, Inc., Astellas.resultsdisclosure@astellas.com

Clinical Trial Disclosure, Astellas Pharma Global Devlopment, Inc., Astellas.resultsdisclosure@astellas.com

No

No

Yes

Final

26 Nov 2012

No

Yes

26 Nov 2012

Yes

The primary objective of this study is to determine the objective response rate (ORR) of single-agent erlotinib versus oral etoposide in patients with recurrent paediatric ependymoma.

This clinical study was written, conducted and reported in accordance with the protocol, ICH GCP Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal and/or regional legislation related to the privacy and protection of personal information. The study was designed to consider stopping early at an interim analysis due to lack of efficacy, minimizing additional patient exposure to treatment that is unlikely to provide benefit.

27 Sep 2010

Yes

Yes

United Kingdom: 4

Canada: 8

United States: 13

25

4

0

0

0

0

12

8

5

0

0

Overall Study (overall period)

Randomised - controlled

Yes

Erlotinib

OSI-774

Tablet

Oral use

Erlotinib was to 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. Erlotinib was provided as tablets containing erlotinib hydrochloride equivalent to 150, 100 and 25 mg of erlotinib.

Etoposide

Capsule, soft

Oral use

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.

Erlotinib

Etoposide

Erlotinib

Etoposide

Objective response is defined as a best overall response of CR (complete response) or PR (partial response), 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.

Primary

From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.

Erlotinib v Etoposide

25

Pre-specified

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. Due to the low number of participants, data cannot be calculated and is denoted as "99999" as applicable.

Secondary

From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide

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.

Secondary

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 SD (stable disease): 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 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.

Secondary

From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.

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. Due to low number of events, upper limit cannot be calculated and is denoted as "99999."

Secondary

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.

Secondary

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, PR, 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. Due to the low number of events, data cannot be calculated and is denoted as "99999" as applicable.

Secondary

From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days 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. Due to the low number of events, overall survival cannot be reported in days, instead presented as the number of participants who died.

Secondary

From the 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

An AE was defined as any untoward medical occurrence in a study participant and did not necessarily have a causal relationship with the study treatment. Clinically significant vital sign aseessments, 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 relaed or not related.

Secondary

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.

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 the steady state using sparse sampling.

Secondary

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 (Cmax) was measured at steady on Day 14 using sparse sampling.

Secondary

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.

Secondary

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.

Secondary

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 distribtuion (Vz/F) of erlotinib was measured at steady state on day 14 using sparse sampling.

Secondary

Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose

From the date of first dose of study drug until 30 days after last dose. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.

13.0

Erlotinib

Etoposide