Clinical trial NCT00526669: Study For Patients With Untreated Gastric Cancer Who Will Receive Capecitabine And Lapatinib
Official title: An Exploratory, Phase II Trial to Determine the Association of Lapatinib Induced Fluoropyrimidine Gene Changes With Efficacy Parameters of Lapatinib and Capecitabine in First Line Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms, Gastrointestinal Tract
Keywords: tumor biopsy
capecitabine
first line
Gastro Esophageal (GE) Junction Cancer
Gastric cancer
newly diagnosed
GE junction
lapatinib
metastatic or unresectable
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-09-10
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will determine if changes in expression of markers involved in the 5-FU pathways are associated with response to treatment with the combination of lapatinib and capecitabine independent of tumor erbB2 status.


Eligibility criteria: Inclusion Criteria:

* Has signed inform consent
* Untreated, newly diagnosed, advanced metastatic or unresectable gastric cancer, including the gastro-esophageal junction
* Tumor accessible to and patient consent for endoscopic biopsy at study start and after 7 days of single agent Lapatinib
* Measurable disease according to RECIST criteria
* Male or female \> or = 18 years of age
* Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram
* must have adequate organ function as defined by baseline laboratory values

Exclusion Criteria:

* Gastric carcinoid, sarcomas, or squamous cell cancer
* Pregnant or lactating females
* Intractable nausea, vomiting, or gastro intestinal obstruction requiring decompression and drainage with a gastric tube or nasogastric suction.
* patients who require continuous enteral feeding
* Malabsorption syndrome or uncontrolled inflammatory GI disease (Crohn's or ulcerative colitis
* Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure

Primary outcomes:
measure: Change From Start of Run-in Period in Biomarker Expression Levels at Day 0
timeFrame: evaluated at baseline and after 7 days of study treatment
measure: Response Rate (Measured as the Percentage of Participants With Response [Complete Response or Partial Response])
timeFrame: From Baseline (Day 0) until disease progression or death due to any cause evaluated every 6 or 12 weeks (up to approximately 85 weeks)
measure: Percentage of Participants (Par.) With 5-month Progression-free Survival (PFS)
timeFrame: From initial treatment up to 24 weeks (next available assessment after the 5-month assessment for progressive disease)
Secondary outcomes:
measure: PFS
timeFrame: From Baseline (Day 0) until disease progression or death due to any cause (up to approximately 85 weeks)
measure: Overall Survival (OS)
timeFrame: From Baseline (Day 0) until death due to any cause evaluated at approximately 12 months (up to approximately 100 weeks)
measure: Time to Progression (All Deaths Are Treated as Competing Risk)
timeFrame: From Baseline (Day 0) until disease progression or death due to any cause (up to approximately 85 weeks)
measure: Time to Progression (All Deaths Due to Non-PD Are Treated as Competing Risk)
timeFrame: From Baseline (Day 0) until disease progression or death due to any cause (up to approximately 85 weeks)
measure: Time to Response
timeFrame: Baseline (Day 0) until first documented evidence of response (up to approximately 60 weeks)
measure: Duration of Response
timeFrame: From date of first documented evidence of response until the date of first documented sign of disease progression or death due to any cause (up to approximately 78 weeks)
measure: Number of Participants in the Indicated Categories for Best Overall Response (BOR)
timeFrame: From Baseline (Day 0) until disease progression or death due to any cause (up to approximately 85 weeks)
measure: Number of Participants With Change From Baseline (Measured as Any Grade Increase [AGI], Increase to Grade 3 [ItoG3], and Increase to Grade 4 [ItoG4]) in Toxicity Grades for Albumin at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Alkaline Phosphatase (ALP) at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Aspartate Aminotransferase (AST) at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4 ) in Toxicity Grades for Alanine Aminotransferase (ALT) at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Total Bilirubin at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Calcium at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Creatinine at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Glucose at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Potassium at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Magnesium at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Sodium at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Hemoglobin at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Lymphocytes at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Total Neutrophils at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Platelet Count at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
measure: Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for White Blood Cell (WBC) Count at the Indicated Time Points
timeFrame: Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Shreveport
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Ann Arbor
country: United States
facility: GSK Investigational Site
state: Michigan
city: Southgate
country: United States
facility: GSK Investigational Site
state: Michigan
city: Jefferson City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Hwasun
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon, Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Astrakhan
country: Russian Federation
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Ufa,
country: Russian Federation
facility: GSK Investigational Site
city: Changhua
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: LaBonte MJ, Yang D, Zhang W, Wilson PM, Nagarwala YM, Koch KM, Briner C, Kaneko T, Rha SY, Gladkov O, Urba SG, Sakaeva D, Pishvaian MJ, Hsieh RK, Lee WP, Lenz HJ. A Phase II Biomarker-Embedded Study of Lapatinib plus Capecitabine as First-line Therapy in Patients with Advanced or Metastatic Gastric Cancer. Mol Cancer Ther. 2016 Sep;15(9):2251-8. doi: 10.1158/1535-7163.MCT-15-0908. Epub 2016 Jun 20.