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

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

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: foretinib (formerly GSK1363089 or XL880)

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Greenbrae, California, United States, 94904-2007
      • GSK Investigational Site
    • San Francisco, California, United States, 94115
      • GSK Investigational Site
    • Stanford, California, United States, 94305
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • GSK Investigational Site
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • GSK Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • GSK Investigational Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • GSK Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • GSK Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • GSK Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5/9 dosing; 240 mg of foretinib on a 5 day on / 9 day off regimen every 14 days.	Drug: foretinib (formerly GSK1363089 or XL880); 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; Other Names: GSK1363089 (formerly XL880)
Experimental: daily dosing; 80 mg foretinib on a daily dosing regimen	Drug: foretinib (formerly GSK1363089 or XL880); 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; Other Names: GSK1363089 (formerly XL880)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Choueiri TK, Vaishampayan U, Rosenberg JE, Logan TF, Harzstark AL, Bukowski RM, Rini BI, Srinivas S, Stein MN, Adams LM, Ottesen LH, Laubscher KH, Sherman L, McDermott DF, Haas NB, Flaherty KT, Ross R, Eisenberg P, Meltzer PS, Merino MJ, Bottaro DP, Linehan WM, Srinivasan R. Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma. J Clin Oncol. 2013 Jan 10;31(2):181-6. doi: 10.1200/JCO.2012.43.3383. Epub 2012 Dec 3.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2006
• Primary Completion (Actual): August 18, 2010
• Study Completion (Actual): August 18, 2010

Study Registration Dates

• First Submitted: July 29, 2008
• First Submitted That Met QC Criteria: July 30, 2008
• First Posted (Estimate): July 31, 2008

Study Record Updates

• Last Update Posted (Actual): December 11, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: c-Met; Papillary Renal Cell Carcinoma(PRC); Sporadic papillary renal cell carcinoma,; Clear cell renal carcinoma; Hereditary papillary renal cell carcinoma,
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: MET111644

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: MET111644
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: MET111644
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: MET111644
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: MET111644
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: MET111644
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: MET111644
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register