Phase 2 Study of GSK1363089 (Formerly XL880) in Adults Wi... | NCT00725764

NCT00725764

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Single Arm	Experimental	Participants who qualified for study entry received 240 mg of GSK1363089 (foretinib) on a 5-day on 9-day off schedule every 2 weeks.	Drug: GSK1363089 (foretinib)

Name	Type	Description	Arm Group Labels	Other Names
GSK1363089 (foretinib)	Drug	Multitargeted tyrosine kinase inhibitor	Single Arm

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Achieving Best Overall Response	Best overall response was assessed by the investigator per response evaluation criteria in solid tumors (RECIST). Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Tumor size was recorded at Baseline, and tumor response were recorded approximately every 8 weeks. Tumor response were classified by the investigator using RECIST criteria participant's best response whether observed in the study treatment period or the treatment extension period was considered. The best overall response was the best response recorded from the start of treatment until disease progression/recurrence. Number of participants who achieved best overall response were recorded.	Approximately up to 1 year
Percentage of Participants With Objective Response Rate (ORR)	ORR was defined as the proportion of participants achieving best overall response of confirmed CR or PR divided by the total number of participants who received treatment. Per RECIST v1.0 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; Partial Response PR, >=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR. Participants were evaluated for tumor response per RECIST. Percentage of participants with ORR were reported.	Approximately up to 1 year
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

Secondary Outcomes

Measure	Description	Time Frame
Duration of Progression-free Survival	Progression-free survival was defined as the duration from the date of first dose to the date of disease progression or date of death without documented progression or date of study termination + 1. The start of confounding anticancer therapy was not treated as a censoring event. Time to progression or death was censored at the study termination date or at the analysis cutoff date, if earlier.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The subject has a histologically or cytologically confirmed diagnosis of SCCHN and
has recurrent and/or metastatic disease
is not eligible for curative intent surgery or radiotherapy
has no history of uncontrolled tumor bleeding including hemoptysis in patients with documented pulmonary metastasis.
The subject has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as =20 mm with conventional techniques, or as =10 mm with spiral computerized tomography (CT) scan.
Subject is capable of swallowing capsules.
Fifteen unstained slides of tumor tissue, archival or fresh, or paraffin block are available, and there - confirmation that samples have been sent for analysis at the central laboratory.
The subject is at least 18 years old.
The subject has an Eastern Cooperative Oncology Group (ECOG) performance status =1.
In the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level =20 µg/dL (552 nmol/L) 30-90 minutes after injection of ACTH.
The subject has organ and marrow function as follows: absolute neutrophil count (ANC) =1500/mm3, platelets =100,000/mm3, hemoglobin =9 g/dL, bilirubin =1.5 mg/dL, serum creatinine =1.5 mg/dL and/or calculated creatinine clearance =60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 times the upper limit of normal if no liver involvement or =5 times the upper limit of normal with liver involvement.
The subject has signed the informed consent document.
Sexually active subjects must use a medically accepted method of contraception during the course of the study.
Female patients of childbearing potential must have a negative pregnancy test at enrollment.
The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed =5 years ago, and has had no evidence of disease for 5 years prior to screening for this study).

Exclusion Criteria:

The subject has received radiation to >25% of his or her bone marrow within 30 days of GSK1363089 treatment.
The subject has received an investigational drug within 30 days (or <5.5 half lives) of the first dose of study drug.
The subject has received more than one regimen of systemic anticancer therapy for disease that has recurred or is metastatic. This may include either single-agent or combination cytotoxic chemotherapy with radiotherapy or anti-EGFR treatment (eg, cetuximab). Adjuvant or neoadjuvant systemic chemotherapy does not count as a regimen for recurrent or metastatic disease.
The subject has progressed within 6 months after completion of curative intent (definitive) treatment for localized/locoregionally advanced disease.
The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade =1 from adverse events (AEs) due to investigational drugs or other medications that were administered more than 30 days before study enrollment with the sole exception of persistent Grade 2 peripheral neuropathy in patients who have previously received platinum-based therapy.
The subject has known brain metastases.
The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active alcoholism, or psychiatric illness that would limit compliance with study requirements.
The subject is pregnant or breastfeeding.
The subject is known to be positive for the human immunodeficiency virus (HIV).
The subject has an allergy or hypersensitivity to components of the GSK1363089 formulation.

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Atlanta	Georgia	30309	United States
GSK Investigational Site

References Module

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
MET111646	Dataset Specification	View IPD

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 milligram (mg) capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of progressive disease (PD) and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

GSK1363089 (formerly XL880)

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00059.6± 8.50

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001
Male	BG00013

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG0001

White

Title	Measurements
	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Achieving Best Overall Response

Best overall response was assessed by the investigator per response evaluation criteria in solid tumors (RECIST). Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Tumor size was recorded at Baseline, and tumor response were recorded approximately every 8 weeks. Tumor response were classified by the investigator using RECIST criteria participant's best response whether observed in the study treatment period or the treatment extension period was considered. The best overall response was the best response recorded from the start of treatment until disease progression/recurrence. Number of participants who achieved best overall response were recorded.

safety population comprised of all participants who passed the screening criteria, enrolled in the study, and received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Approximately up to 1 year

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts
Participants	OG00014

Title

Denominators

Categories

Stable Disease

Title	Measurements
	OG0007

Progressive Disease

Title	Measurements
	OG0003

Unable to evaluate

Primary

Percentage of Participants With Objective Response Rate (ORR)

ORR was defined as the proportion of participants achieving best overall response of confirmed CR or PR divided by the total number of participants who received treatment. Per RECIST v1.0 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; Partial Response PR, >=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR. Participants were evaluated for tumor response per RECIST. Percentage of participants with ORR were reported.

Safety Population.

Posted

Number

95% Confidence Interval

Percentage of participants

Approximately up to 1 year

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts

Primary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

Safety Population.

Posted

Count of Participants

Participants

Up to 20 months

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Primary

Number of Participants With Abnormalities of Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 in Laboratory Parameters (Clinical Chemistry and Hematology)

The National Cancer Institute -CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. Number of participants with abnormalities of CTCAE grade 3 in clinical chemistry parameters: alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), phosphate, low sodium and hematology parameters: Leukocyte and Lymphocytes were presented.

Safety Population. Only those participants available at the specified time points were analyzed.

Posted

Count of Participants

Participants

Up to 20 months

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Primary

Number of Participants With Abnormalities in Urinalysis

Urinalysis parameters like appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and occult blood were performed. Number of participants with abnormalities are reported. In case of no abnormalities observed then it is reported as zero.

Safety population.

Posted

Count of Participants

Participants

Week 5 [Day 29]

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts
Participants

Secondary

Duration of Progression-free Survival

Progression-free survival was defined as the duration from the date of first dose to the date of disease progression or date of death without documented progression or date of study termination + 1. The start of confounding anticancer therapy was not treated as a censoring event. Time to progression or death was censored at the study termination date or at the analysis cutoff date, if earlier.

Safety Population.

Posted

Median

Full Range

Months

Approximately up to 1 year

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts
Participants

Secondary

Duration of Overall Survival

Overall survival was defined as the duration from the date of the first dose to the date of death. The start of a confounding anticancer therapy was treated as a censoring event. Every effort made to follow participant's until death. Time to death was censored at the date of the latest participant contact or at the analysis cutoff date, if earlier. Kaplan-Meier method was used to estimate the overall survival distribution.

Safety Population.

Posted

Median

Full Range

Months

Approximately up to 1 year

ID	Title	Description
OG000	Foretinib 240 mg	This study consisted of a pre-treatment Period (screening and baseline evaluations), 8 week study treatment period, an optional treatment extension period, and a post-treatment period (including an end-of-treatment visit and an extended follow-up period). In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Secondary

Duration of Stable Disease

Per RECIST v1.0 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; Partial Response PR, >=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR. Duration of stable disease was defined as the time between the date of first dose of study drug and the first occurrence of 1 of the events: Tumor progression per RECIST as assessed by the investigator, Termination of study drug because of disease progression, Death due to disease progression, Disease progression as documented on the participant follow-up status form, Initiation of subsequent anticancer therapy.

Safety Population. Analysis set included only participants whose best overall response was not disease progression.

Posted

Median

Full Range

Months

Approximately up to 1 year

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Secondary

Percentage Participants With Disease Stabilization Rate

Disease stabilization rate was defined as the proportion of participants for whom the best overall response was a PR, CR, or stable disease. percentage participants with disease stabilization rate were presented.

Safety Population

Posted

Number

95% Confidence Interval

percentage of participants

Approximately up to 1 year

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts
Participants	OG000

Secondary

Maximum Plasma Concentration (Cmax) of Foretinib in Participants With Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Plasma samples for pharmacokinetic analysis were planned to be drawn at time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing) of each treatment cycle, however these analyses were not completed. Cmax was defined as maximal measured plasma concentration over the time span specified. Data was not collected for this endpoint.

Safety population. Data was not collected for this endpoint.

Posted

Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts

Secondary

Time to Maximum Plasma Concentration (Tmax) of Foretinib in Participants With SCCHN

tmax was defined as the time to the maximum or "peak" concentration of a drug observed after multiple administration. Blood samples were planned to be obtained during the time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). However these analyses were not completed. Data was not collected for this endpoint.

Safety population. Data was not collected for this endpoint.

Posted

Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts
Participants

Secondary

Area Under the Concentration-time Curve (AUC) of Foretinib in Participants With SCCHN

AUC was defined as area under the plasma concentration vs. time curve. Blood samples were planned to be collected on time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). However these analyses were not completed. Data was not collected for this endpoint.

Safety population. Data was not collected for this endpoint.

Posted

Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts
Participants

Secondary

Elimination Half-life (t1/2) of Foretinib in Participants With SCCHN

t1/2 was defined as the time to when half of the total amount of a particular substance is eliminated from the body. Blood samples were planned to be obtained during indicated time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). However these analyses were not completed. Data was not collected for this endpoint.

Safety population. Data was not collected for this endpoint.

Posted

Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts
Participants

Secondary

Apparent Oral Clearance

Blood samples were planned to be obtained during indicated time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). Data for apparent oral clearance was not derived as pharmacokinetic analysis was not completed. Data was not collected for this endpoint.

Safety population. Data was not collected for this endpoint.

Posted

Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts
Participants

Secondary

Apparent Volume of Distribution

Blood samples were planned to be obtained during indicated time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). Data for apparent volume of distribution was not derived as pharmacokinetic analysis was not completed. Data was not collected for PK analysis.

Safety population. Data was not collected for this endpoint.

Posted

Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose

ID	Title	Description
OG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Foretinib 240 mg	In each treatment period, participants received foretinib 240 mg capsules orally on Days 1-5 of every 14-day cycle. Participants fasted 2 hours before to 1 hour after each dose. Each treatment cycle was 2 weeks. The 8-week study treatment period consisted of four 2-week treatment cycles. In the absence of PD and unacceptable toxicity, participants may have received foretinib treatment on the same dosing schedule for up to 1 year at the discretion of the investigator, and beyond 1 year with the approval of the sponsor while participating in this study. During the treatment extension period, participants continued to receive foretinib on Days 1 through 5 followed by a 9-day observation period.	7	14	12	14	14	14

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Odynophagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Trismus	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Obstructive airways disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Haemorrhage	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected14 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected14 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected14 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Gingival pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Glossodynia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Haematochezia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Odynophagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Oral discomfort	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Oral pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Stomach discomfort	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Swollen tongue	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Tongue disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0007 affected14 at risk
Mucosal inflammation	General disorders	MedDRA	Systematic Assessment	EG0004 affected14 at risk
Pain	General disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Chills	General disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Facial pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Local swelling	General disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Temperature intolerance	General disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0004 affected14 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0004 affected14 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0004 affected14 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Blood calcium decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Heart rate increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Heart sounds abnormal	Investigations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
International normalised ratio increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Prothrombin time prolonged	Investigations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected14 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Neck mass	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Soft tissue necrosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Trismus	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0003 affected14 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0003 affected14 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Blister	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Skin reaction	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Telangiectasia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0004 affected14 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected14 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Amnesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Memory impairment	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected14 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Bronchial secretion retention	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dyspnoea paroxysmal nocturnal	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Painful respiration	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Herpes zoster	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Localised infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Oral candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Otitis media	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Postoperative wound infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Tooth abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0004 affected14 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0003 affected14 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0003 affected14 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0003 affected14 at risk
Panic attack	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0005 affected14 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected14 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Ear pain	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Procedural site reaction	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Wound secretion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Dysuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Haematuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk
Hypothyroidism	Endocrine disorders	MedDRA	Systematic Assessment	EG0001 affected14 at risk

ID	Term
D006258	Head and Neck Neoplasms

ID	Term
C544831	GSK 1363089

Title	Measurements
	OG0001

Units	Counts
Participants	OG00014

Units	Counts
Participants	OG00014

Units	Counts
Participants	OG0007