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

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ClinicalTrials.gov Identifier: NCT00726323
Recruitment Status : Completed
First Posted : July 31, 2008
Results First Posted : December 11, 2017
Last Update Posted : December 11, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Renal Cell Drug: foretinib (formerly GSK1363089 or XL880) Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of the c-MET RTK Inhibitor XL880 in Subjects With Papillary Renal-Cell Carcinoma
Actual Study Start Date : June 30, 2006
Actual Primary Completion Date : August 18, 2010
Actual Study Completion Date : August 18, 2010


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 Name: 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 Name: GSK1363089 (formerly XL880)



Primary Outcome Measures :
  1. Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.0 [ Time Frame: At the end of forth year ]
    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.


Secondary Outcome Measures :
  1. Disease Stabilization Rate Over Period [ Time Frame: Up to 4 years ]
    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.

  2. Progression Free Survival (PFS) [ Time Frame: At the end of forth year ]
    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.

  3. Time to Response (TTR) Over Period [ Time Frame: Up to 4 years ]
    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.

  4. Duration of Response (DOR) [ Time Frame: Up to 4 years ]
    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.

  5. Duration of Stable Disease (SD) [ Time Frame: Up to 4 years ]
    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.

  6. Overall Survival [ Time Frame: Up to 4 years ]
    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.

  7. Number of Participants With Change in Common Terminology Criteria for Adverse Events (CTCAE) Grade of Clinical Chemistry Parameters Over Period [ Time Frame: Up to 4 years ]
    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.

  8. Number of Participants With Change in CTCAE Grade of Hematological Parameters Over Period (Only Worst Case) [ Time Frame: Up to 4 years ]
    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.

  9. Number of Participants With Adverse Events, Serious Adverse Events, and Deaths [ Time Frame: Up to 4 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00726323


Locations
United States, California
GSK Investigational Site
Greenbrae, California, United States, 94904-2007
GSK Investigational Site
San Francisco, California, United States, 94115
GSK Investigational Site
Stanford, California, United States, 94305
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
United States, Maryland
GSK Investigational Site
Bethesda, Maryland, United States, 20892
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02115
United States, Michigan
GSK Investigational Site
Detroit, Michigan, United States, 48201
United States, New Jersey
GSK Investigational Site
New Brunswick, New Jersey, United States, 08901
United States, Ohio
GSK Investigational Site
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37232
United States, Texas
GSK Investigational Site
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Additional Information:
Study Data/Documents: Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: MET111644
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: MET111644
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: MET111644
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: MET111644
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: MET111644
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: MET111644
For additional information about this study please refer to the GSK Clinical Study Register

Publications:
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00726323     History of Changes
Obsolete Identifiers: NCT00345423
Other Study ID Numbers: MET111644
First Posted: July 31, 2008    Key Record Dates
Results First Posted: December 11, 2017
Last Update Posted: December 11, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: http://

Keywords provided by GlaxoSmithKline:
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:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases