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

• Sponsor: OSI Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01247922
• Collaborator: (none)
• Enrollment: 4
• Locations: 21
• Arm: 1
• Actual Duration (Months): 15.7
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ependymoma	Drug: Erlotinib	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label Phase 2 Study of Single-agent Erlotinib for Patients With Pediatric Ependymoma Previously Treated With Oral Etoposide in Protocol OSI-774-205
• Actual Study Start Date: May 23, 2011
• Actual Primary Completion Date: Sep 13, 2012
• Actual Study Completion Date: Sep 13, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. Median Treatment Duration [From first dose of study drug up to last dose of study drug (The mean treatment duration was 170.5 days)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 21 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• OSI Pharmaceuticals

Investigators

• Study Director: Medical Monitor, Astellas Pharma Global Development

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Link to results on Astellas Clinical Study Results website

Publications

None provided.

• Responsible Party: OSI Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01247922
• Other Study ID Numbers: OSI-774-206; 2010-023478-38
• First Posted: Nov 25, 2010
• Last Update Posted: Jun 19, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by OSI Pharmaceuticals: Pediatric Ependymoma; Ependymoma; Tarceva; Erlotinib
• Additional relevant MeSH terms: Ependymoma; Erlotinib Hydrochloride

Study Results

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 Detail	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.

Arm/Group Title	Erlotinib
Arm/Group Description	Participants who received erlotinib in a continuous oral dose of 85 mg/m^2 per day until dose modification, interruption or study discontinuation occurred.
Period Title: Overall Study
STARTED	4
Treated	4
COMPLETED	0
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Erlotinib
Arm/Group Description	Participants who received erlotinib in a continuous oral dose of 85 mg/m^2 per day until dose modification, interruption or study discontinuation occurred.
Overall Participants	4
Age (Count of Participants)
<=18 years	4 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 25%
Male	3 75%
Race/Ethnicity, Customized (participants) [Number]
White	3 75%
Asian-Indian subcontinent	1 25%

Outcome Measures

1. Primary Outcome

Title	Safety Assessed Through Evaluation of Physical Examinations, Vital Signs, Clinical Laboratory Tests, and Adverse Events (AEs)
Description	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)

Outcome Measure Data

Analysis Population Description

The analysis population is the Safety Analysis Set (SAF) consisted of all enrolled patients who received at least 1 dose of study drug.

Arm/Group Title	Erlotinib
Arm/Group Description	Participants who received erlotinib in a continuous oral dose of 85 mg/m^2 per day until dose modification, interruption or study discontinuation occurred.
Measure Participants	4
Any TEAE	4 100%
With at least 1 SAE	2 50%
With at least 1 treatment-related SAE	0 0%
Discontinued study due to treatment-related AEs	0 0%
Died on treatment or within 30 days	1 25%

2. Secondary Outcome

Title	Best Overall Response
Description	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.)

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Erlotinib
Arm/Group Description	Participants who received erlotinib in a continuous oral dose of 85 mg/m^2 per day until dose modification, interruption or study discontinuation occurred.
Measure Participants	4
Complete response	0 0%
Partial response	0 0%
Minor response	0 0%
Stable disease	2 50%
Disease progression	2 50%

3. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

SAF

Arm/Group Title	Erlotinib
Arm/Group Description	Participants who received erlotinib in a continuous oral dose of 85 mg/m^2 per day until dose modification, interruption or study discontinuation occurred.
Measure Participants	4
Median (Full Range) [days]	91.0

Adverse 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.)
Arm/Group Title	Erlotinib
Arm/Group Description	Participants who received erlotinib in a continuous oral dose of 85 mg/m^2 per day until dose modification, interruption or study discontinuation occurred.
All Cause Mortality
	Erlotinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Erlotinib
	Affected / at Risk (%)	# Events
Total	2/4 (50%)
General disorders
Brain death	1/4 (25%)
Nervous system disorders
Convulsion	1/4 (25%)
Neuropathy peripheral	1/4 (25%)
VIIth nerve paralysis	1/4 (25%)
Other (Not Including Serious) Adverse Events
	Erlotinib
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Eye disorders
Vision blurred	1/4 (25%)
Gastrointestinal disorders
Abdominal pain	1/4 (25%)
Abdominal pain upper	1/4 (25%)
Diarrhoea	1/4 (25%)
Dyspepsia	1/4 (25%)
Nausea	1/4 (25%)
Vomiting	1/4 (25%)
General disorders
Fatigue	3/4 (75%)
Pain	1/4 (25%)
Pyrexia	1/4 (25%)
Infections and infestations
Nasopharyngitis	1/4 (25%)
Pneumonia	1/4 (25%)
Rash pustular	1/4 (25%)
Investigations
Blood bilirubin increased	1/4 (25%)
Weight decreased	1/4 (25%)
Weight increased	1/4 (25%)
Metabolism and nutrition disorders
Decreased appetite	2/4 (50%)
Musculoskeletal and connective tissue disorders
Bone pain	1/4 (25%)
Muscular weakness	1/4 (25%)
Posture abnormal	1/4 (25%)
Nervous system disorders
Dysarthria	1/4 (25%)
Headache	3/4 (75%)
Partial seizures	1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Cough	2/4 (50%)
Dysphonia	1/4 (25%)
Epistaxis	1/4 (25%)
Oropharyngeal pain	2/4 (50%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/4 (25%)
Ingrowing nail	1/4 (25%)
Rash	1/4 (25%)
Rash maculo-papular	1/4 (25%)
Skin striae	1/4 (25%)
Vascular disorders
Peripheral coldness	1/4 (25%)

Limitations/Caveats

Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 30 days prior to publication for review and comment. Sponsor may delay the publication for an additional to 60 days to seek patent protection.