Trial Outcomes & Findings for A Phase II Study of GSK1363089 (Formerly XL880) for Papillary Renal-Cell Carcinoma (PRC) (NCT NCT00726323)

Last Updated: 2017-12-11

Results Overview

Overall response rate is the percentage of participants for whom the best overall response to the study drug was a confirmed partial response (PR) or confirmed complete response (CR). Best overall response and its associated confirmation criteria, RECIST; Version 1.0) was based on the Investigator's assessment of the target and non target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

74 participants

Primary outcome timeframe

At the end of forth year

Results posted on

2017-12-11

Participant Flow

This study was conducted from 30 June 2006 till 18 August 2010 across 10 centers in the United States (US). A total of 60 participants with papillary renal-cell carcinoma (PRC) were planned to be enrolled.

A total of 74 participants with PRC were enrolled in the study.

Participant milestones

Participant milestones
Measure	Intermittent 5 & 9 Dosing Regimen Eligible participants received oral foretinib bisphosphate 240 milligrams (mg) on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Overall Study STARTED	37	37
Overall Study COMPLETED	0	6
Overall Study NOT COMPLETED	37	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Intermittent 5 & 9 Dosing Regimen Eligible participants received oral foretinib bisphosphate 240 milligrams (mg) on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Overall Study Withdrawal by Subject	3	1
Overall Study Physician Decision	1	0
Overall Study Progressive disease	23	16
Overall Study Clinical progression	0	3
Overall Study Adverse Event	9	9
Overall Study Death	1	0
Overall Study Participant wished to discontinue	0	1
Overall Study Metastatic lesions inferred cyst	0	1

Baseline Characteristics

A Phase II Study of GSK1363089 (Formerly XL880) for Papillary Renal-Cell Carcinoma (PRC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intermittent 5 & 9 Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Total n=74 Participants Total of all reporting groups
Age, Continuous	55.1 Years STANDARD_DEVIATION 11.84 • n=5 Participants	56.2 Years STANDARD_DEVIATION 14.32 • n=7 Participants	55.6 Years STANDARD_DEVIATION 13.06 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	29 Participants n=7 Participants	59 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	32 Participants n=5 Participants	32 Participants n=7 Participants	64 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At the end of forth year

Population: The Safety population included all participants who passed the screening criteria, were enrolled in the study and received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.0	13.5 Percentage of participants Interval 4.5 to 28.8	13.5 Percentage of participants Interval 4.5 to 28.8

SECONDARY outcome

Timeframe: Up to 4 years

Population: Safety population

The percentage of participants for whom the best overall response was a confirmed PR, confirmed CR, or stable disease. Exact confidence intervals were obtained using the Clopper-Pearson method. Exact confidence intervals were obtained using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Disease Stabilization Rate Over Period	91.9 Percentage of participants Interval 78.1 to 98.3	83.8 Percentage of participants Interval 68.0 to 93.8

SECONDARY outcome

Timeframe: At the end of forth year

Population: Safety population

Progression free survival is defined as the time between the date of first dose of study drug and the date of the first occurrence of either tumor progression per RECIST or clinical assessment of progression as assessed by Investigator or Death due to any cause, whichever occurs the first. For participants who did not reach an event (disease progression or death) at the time of data cutoff, PFS was censored at the date of the last available tumor measurement. For participants who did not have any post-baseline tumor assessments, PFS was right censored at Day 1. For any participants who received subsequent anticancer therapy, PFS was right censored at the date of last adequate tumor assessment on or prior to the date of anticancer initiation. For any participants, who died or progressed after an extended follow-up, PFS was censored at the date of last adequate assessment prior to the extended loss to follow-up.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Progression Free Survival (PFS)	11.56 Months Interval 5.78 to 16.99	9.07 Months Interval 5.78 to 10.91

SECONDARY outcome

Timeframe: Up to 4 years

Population: Safety population

Time to response is the time between the date of first dose of study drug and the date of first response (for participants who had overall responses that were later confirmed as CR/PR). For the 6 participants in the daily dosing cohort who did not reach a response as of data cutoff, the time to response was censored at the date of the last visit. The median time to response was not estimable in either of the dosing cohorts or in the overall safety population using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Time to Response (TTR) Over Period	NA Months Interval 22.05 to The median time to response was not estimable.	NA Months Interval 12.88 to The median time to response was not estimable.

SECONDARY outcome

Timeframe: Up to 4 years

Population: Safety Population- All Objective Responders (those who did not reach an event by the time of data cut-off as defined in protocol)

Duration of response is defined as the time between the date of first response (later confirmed CR or confirmed PR) and the date of the first occurrence of one of the events as tumor progression per RECIST as assessed by Investigator, termination of the study drug due to disease progression, death due to any cause, disease progression as documented on the follow-up or participant status form Initiation of subsequent anticancer therapy. For the 6 participants in the daily dosing cohort who did not reach a response as of data cutoff, the duration of response was censored at the date of the last available tumor measurement.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=5 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=5 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Duration of Response (DOR)	20.50 Months Interval 5.55 to 20.5	18.46 Months Interval 5.55 to 18.46

SECONDARY outcome

Timeframe: Up to 4 years

Population: Safety population. All participants with Best overall response, not progressive disease were considered.

Duration of SD is defined as the time between the date of first dose of study drug and the date of the first occurrence of one of the tumor progression per RECIST as assessed by Investigator, termination of the study drug due to disease progression, death due to disease progression, or disease progression as documented on the follow-up participants status form Initiation of subsequent anticancer therapy. For the 6 participants in the daily dosing cohort who did not reach a response as of data cutoff, the duration of stable disease was right censored at the date of the last available tumor measurement.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=34 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=31 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Duration of Stable Disease (SD)	12.88 Months Interval 6.14 to 16.99	9.26 Months Interval 7.16 to 10.84

SECONDARY outcome

Timeframe: Up to 4 years

Population: Safety population

Overall survival, which is defined as the time between the date of first dose of study drug and the date of death (due to any cause). For participants who were alive at the time of data cutoff, duration of overall survival was right censored at the date of last contact. Duration of overall survival = date of death/censoring - date of first dose +1. Percentiles and confidence intervals are calculated using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Overall Survival	NA Months Interval 11.83 to The median survival time was not estimable.	NA Months The median survival time was not estimable.

SECONDARY outcome

Timeframe: Up to 4 years

Population: Safety population

The worst case overall common terminology criteria for adverse events (CTCAE) grade shift post Baseline for each parameter was mentioned. Only worst case scenarios are presented. CTCAE grading was done as per intensity namely mild moderate severe life-threatening or Death. Analysis was done for Alanine aminotransferases (ALT), aspartate aminotransferases (AST), Albumin, alkaline phosphatase (ALP), calcium, sodium, potassium, glucose, amylase, carbon dioxide, phosphate, gamma glutamyl transferases (GGT), and triglycerol lipase. High (H) levels and low (L) levels were measured.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period ALT, Grade 0 to 1	24 Participants	21 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period ALT, Grade 0 to 3	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Albumin, Grade 1 to 2	6 Participants	5 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Albumin, Grade 1 to 3	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period ALP, Grade 0 to 1	12 Participants	16 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period AST, Grade 2 to 3	1 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Carbon di oxide, Grade 0 to 1	11 Participants	9 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Creatinine, Grade 0 to 1	6 Participants	11 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Creatinine, Grade 1 to 0	1 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period GGT, Grade 1 to 0	0 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Phosphate, Grade 0 to 2	8 Participants	10 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Phosphate, Grade 2 to 4	1 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Sodium, L, Grade 0 to 3	3 Participants	6 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Albumin, Grade 0 to 3	1 Participants	2 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period ALT, Grade 0 to 2	4 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period ALT, Grade 1 to 2	1 Participants	2 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Albumin, Grade 0 to 1	9 Participants	12 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Albumin, Grade 0 to 2	8 Participants	11 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period ALP, Grade 0 to 2	1 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period ALP, Grade 0 to 3	0 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period ALP, Grade 0 to 4	0 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period ALP, Grade 1 to 2	0 Participants	2 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Amylase, Grade 0 to 1	9 Participants	6 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Amylase, Grade 0 to 2	1 Participants	2 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Amylase, Grade 0 to 3	1 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Amylase, Grade 1 to 2	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Amylase, Grade 2 to 3	1 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period AST, Grade 0 to 1	23 Participants	27 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period AST, Grade 0 to 2	8 Participants	3 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period AST, Grade 0 to 3	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period AST, Grade 1 to 2	2 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Blilirubin, Grade 0 to 1	7 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Blilirubin, Grade 0 to 3	1 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Blilirubin, Grade 1 to 2	1 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Creatinine, Grade 0 to 2	3 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Creatinine, Grade 0 to 3	2 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Creatinine, Grade 1 to 2	2 Participants	8 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period GGT, Grade 0 to 1	7 Participants	6 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period GGT, Grade 2 to 0	0 Participants	—
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period GGT, Grade 2 to 1	0 Participants	—
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Phosphate, Grade 0 to 1	1 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Phosphate, Grade 0 to 3	13 Participants	8 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Phosphate, Grade 2 to 0	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Phosphate, Grade 2 to 3	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Triglycerol lipase, Grade 0 to 1	6 Participants	9 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Triglycerol lipase, Grade 0 to 2	1 Participants	6 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Triglycerol lipase, Grade 0 to 3	4 Participants	4 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Triglycerol lipase, Grade 0 to 4	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Triglycerol lipase, Grade 1 to 3	1 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Triglycerol lipase, Grade 1 to 4	1 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Triglycerol lipase, Grade 2 to 3	1 Participants	—
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Calcium, L, Grade 0 to 1	12 Participants	14 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Calcium, L, Grade 0 to 2	7 Participants	13 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Calcium, L, Grade 0 to 3	1 Participants	2 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, L, Grade 0 to 1	10 Participants	11 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, L, Grade 0 to 2	1 Participants	4 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, L, Grade 0 to 3	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, L, Grade 1 to 3	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Potassium, L, Grade 0 to 1	5 Participants	2 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Potassium, L, Grade 1 to 0	1 Participants	—
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Sodium, L, Grade 0 to 1	11 Participants	14 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Sodium, L, Grade 1 to 3	1 Participants	—
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Calcium, H, Grade 0 to 1	2 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, H, Grade 0 to 1	16 Participants	10 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, H, Grade 0 to 2	6 Participants	4 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, H, Grade 1 to 0	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, H, Grade 1 to 2	4 Participants	2 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, H, Grade 1 to 3	1 Participants	0 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Glucose, H, Grade 2 to 3	—	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Potassium, H, Grade 0 to 1	5 Participants	11 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Potassium, H, Grade 0 to 2	8 Participants	6 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Potaasium, H, Grade 0 to 3	0 Participants	1 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Potassium, H, Grade 1 to 3	1 Participants	—
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Sodium, H, Grade 0 to 1	6 Participants	7 Participants
Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period Sodium, H, Grade 1 to 0	—	1 Participants

SECONDARY outcome

Timeframe: Up to 4 years

Population: Safety population

CTCAE gradation The worst case overall CTCAE grade shift post Baseline for each parameter was mentioned. Only worst case scenarios are presented. CTCAE grading was done as per intensity namely mild moderate severe life-threatening or Death. Participants were analyzed for hemoglobin, leukocytes, platelets, percentage of lymphocytes, and percentage of neutrophils.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage neutrophils, Grade 0 to 4	0 Participants	1 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage neutrophils, Grade 1 to 0	1 Participants	0 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Platelets, Grade 0 to 1	12 Participants	18 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Platelets, Grade 0 to 2	1 Participants	2 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Hemoglobin, Grade 0 to 1	12 Participants	7 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Hemoglobin, Grade 0 to 2	1 Participants	0 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Hemoglobin, Grade 1 to 2	3 Participants	2 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Hemoglobin, Grade 1 to 3	1 Participants	1 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Hemoglobin, Grade 2 to 1	1 Participants	1 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Leukocytes, Grade 0 to 1	5 Participants	10 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Leukocytes, Grade 0 to 2	2 Participants	0 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Leukocytes, Grade 1 to 2	1 Participants	—
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Leukocytes, Grade 2 to 0	1 Participants	—
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage lymphocytes, Grade 0 to 1	5 Participants	8 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage lymphocytes, Grade 0 to 2	4 Participants	0 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage lymphocytes, Grade 0 to 3	3 Participants	2 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage lymphocytes, Grade 1 to 0	0 Participants	1 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage lymphocytes, Grade 1 to 2	1 Participants	2 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage lymphocytes, Grade 2 to 0	1 Participants	0 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage lymphocytes, Grade 2 to 1	0 Participants	1 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage lymphocytes, Grade 2 to 3	3 Participants	0 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage lymphocytes, Grade 3 to 4	1 Participants	—
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage neutrophils, Grade 0 to 1	4 Participants	4 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Percentage neutrophils, Grade 0 to 2	1 Participants	1 Participants
Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) Platelets, Grade 1 to 2	—	1 Participants

SECONDARY outcome

Timeframe: Up to 4 years

Population: Safety population

Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. Serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.

Outcome measures

Outcome measures
Measure	Intermittent 5 & 9 Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 240 mg on Days 1 to 5 of every 14-day cycle. Participants continued this schedule for 8 weeks. The treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.	Daily Dosing Regimen n=37 Participants Eligible participants received oral foretinib bisphosphate 80 mg daily of every 14-day cycle. Participants continued this schedule for 8 weeks. treatment drug was supposed to be stopped any time in case of disease progression. All participants were followed-up up to 8 weeks after the last dose of the study drug for tumor assessment.
Number of Participants With Adverse Events, Serious Adverse Events, and Deaths Death	14 Participants	6 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Deaths Any AE	37 Participants	37 Participants
Number of Participants With Adverse Events, Serious Adverse Events, and Deaths Any SAE	20 Participants	22 Participants

Adverse Events

Intermittent 5 & 9 Dosing Regimen

Serious events: 20 serious events

Other events: 37 other events

Deaths: 14 deaths

Daily Dosing Regimen

Serious events: 22 serious events

Other events: 37 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER