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

Study Overview
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Brief Summary
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This clinical study is being conducted at multiple sites to determine the best confirmed response rate, safety, and tolerability of GSK1363089 treatment in papillary renal cell carcinoma. Papillary renal cell carcinoma may be classified into hereditary and sporadic forms; subjects with either classification will be accepted into this study.

Official Title
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A Phase II Study of the c-MET RTK Inhibitor XL880 in Subjects With Papillary Renal-Cell Carcinoma

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: foretinib (formerly GSK1363089 or XL880)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of PRC with metastatic disease or bilateral multifocal renal tumors localized to kidneys. Measurable disease, ECOG performance status of </= 2. Adequate bone marrow reserve, hepatic, renal, and cardiovascular function. Exclusion Criteria: Radiation to >/=25% of bone marrow within 14 days of GSK1363089, more than 1 prior anti-cancer therapy, received prior treatment with a c-met inhibitor, brain metastases, Any uncontrolled intercurrent illness, Pregnant or breastfeeding, HIV positive

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5/9 dosing<br>240 mg of foretinib on a 5 day on / 9 day off regimen every 14 days. | Drug: foretinib (formerly GSK1363089 or XL880)<br>* treatment with oral foretinib on one of 2 dosing regimens: 240 mg on a 5 day on / 9 day off schedule every 14 days, or 80 mg on a daily dosing schedule<br>* Other names: GSK1363089 (formerly XL880);|
| Experimental: daily dosing<br>80 mg foretinib on a daily dosing regimen | Drug: foretinib (formerly GSK1363089 or XL880)<br>* treatment with oral foretinib on one of 2 dosing regimens: 240 mg on a 5 day on / 9 day off schedule every 14 days, or 80 mg on a daily dosing schedule<br>* Other names: GSK1363089 (formerly XL880);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.0 | 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. | At the end of forth year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Stabilization Rate Over Period | 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. | Up to 4 years | 
| Progression Free Survival (PFS) | 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. | At the end of forth year | 
| Time to Response (TTR) Over Period | 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. | Up to 4 years | 
| Duration of Response (DOR) | 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. | Up to 4 years | 
| Duration of Stable Disease (SD) | 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. | Up to 4 years | 
| Overall Survival | 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. | Up to 4 years | 
| Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period | 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. | Up to 4 years | 
| Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) | 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. | Up to 4 years | 
| Number of Participants With Adverse Events, Serious Adverse Events, and Deaths | 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. | Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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c-Met, Papillary Renal Cell Carcinoma(PRC), Sporadic papillary renal cell carcinoma,, Clear cell renal carcinoma, Hereditary papillary renal cell carcinoma,