Clinical trial NCT00486954: Lapatinib in Combination With Weekly Paclitaxel in Patients With ErbB2 Amplified Advanced Gastric Cancer
Official title: A Randomized, Multicenter, Open-label, Phase III Study of Lapatinib (GW572016) in Combination With Weekly Paclitaxel Versus Weekly Paclitaxel Alone in the Second Line Treatment of ErbB2 Amplified Advanced Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neoplasms, Gastrointestinal Tract
Keywords: lapatinib
paclitaxel
ErbB2
Gastric cancer
Advanced gastric cancer
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-06-15
Enrollment: 273
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: EGF104578 is two-part study (Pilot part/Randomized part).Pilot part is designed to find the optimal (best) doses of lapatinib and paclitaxel when given together,Randomized part is designed to evaluate the overall survival in patients receiving lapatinib and paclitaxel compared to patients receiving only paclitaxel.


Eligibility criteria: Inclusion criteria:

Specific Information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the Investigator's Brochure (IB) Pilot Part

Subjects eligible for enrollment in the Pilot Part of the study must meet all of the following criteria:

* Signed informed consent
* Male or female; ≥ 20 years (at the time of giving consent)
* Any histologically or cytologically confirmed gastric carcinoma independent of tumor ErbB2 status
* Subjects who have received one prior regimen for gastric carcinoma and developed disease progression or recurrence. The regimen must have contained 5-fluoropyrimidine and/or cisplatin
* Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by echocardiogram (ECHO). Multigated acquisition (MUGA) scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive (LVEF of ≥50% required if normal range of LVEF is not provided by institution)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
* Able to swallow and retain oral medication
* Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study
* Washout period from the prior last therapy as follows; Chemotherapy (except for agents below) 4 weeks (I.V) Chemotherapy (except for agents below) 2 weeks (P.O) Trastuzumab, Bevacizumab 4 weeks Mitomycin-C, nitrosourea 6 weeks Radiotherapy, Immunotherapy, Biologic therapy and Surgery (except for minor surgical procedure) 2 weeks
* Willing to complete all screening assessments as outlined in the protocol
* Adequate organ function as defined in Table 2 Baseline Laboratory Values
* Able to be hospitalized for PK analysis during cycle 1
* Life expectancy of at least 12 weeks from the first dose of study treatment)

Randomized Part

Subjects eligible for enrollment in the Randomized Part of the study must meet all of the following criteria:

* Signed informed consent
* Male or female; ≥ 20 years (at the time of giving consent)
* Histologically or cytologically confirmed gastric carcinoma with documented amplification of ErbB2 by fluorescence in situ hybridization (FISH) in primary or metastatic tumor tissue
* Subjects who received one prior regimen for gastric carcinoma and defined as progression disease. The regimen must be containing 5-fluoropyrimidine and/or cisplatin
* Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors)
* Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive (LVEF of ≥50% required if normal range of LVEF is not provided by institution)
* ECOG Performance Status of 0 to 1
* Able to swallow and retain oral medication
* Archived (or Biopsy ) tumor tissue available for FISH testing \[Wolff, 2007\] in central laboratory
* Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study
* Washout period from the prior last therapy as follows; Chemotherapy (except for agents below) 4 weeks (IV) Chemotherapy (except for agents below) 2 weeks (P.O) Trastuzumab, Bevacizumab 4 weeks Mitomycin-C, nitrosourea 6 weeks Radiotherapy, Immunotherapy, Biologic therapy and Surgery (except for minor surgical procedure) 2 weeks
* Willing to complete all screening assessments as outlined in the protocol
* Adequate organ function as defined in Table 2
* Gastrectomy status depending on the result in the Pilot Part
* Life expectancy of at least 12 weeks from the first dose of study treatment

Table 2 Baseline Laboratory Values

SYSTEM LABORATORY (VALUES)

Hematologic:

ANC (absolute neutrophil count)

Hemoglobin:

Platelets (≥ 2.0 × 10\^9/L) (≥ 9 g/dL) (≥ 100 × 10\^9/L) Hepatic Albumin Serum bilirubin AST and ALT (≥ 2.5 g/dL) (≤ 1.25 x ULN) (≤ 2.5 × ULN without liver metastases) (≤ 5 × ULN if documented liver metastases) Renal Serum Creatinine

Calculate Creatinine Clearance (see Section 11.3) (≤ 2.0 mg/dL)

- OR - (≥30 mL/min)

Exclusion criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

* Pregnant or lactating female at anytime during the study
* Planned concurrent anti-cancer therapy (chemotherapy, radiotherapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment
* Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2)
* Peripheral neuropathy of Grade 2 or greater
* Malabsorption syndrome, disease significantly affecting gastrointestinal function. Subjects with ulcerative colitis and Crohn's disease are also excluded
* History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, are eligible
* Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety
* Life threatening infection
* Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
* Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure
* Known history or clinical evidence of central nervous system (CNS) metastasis
* Concurrent treatment with prohibited medications, including herbal remedies and Chinese traditional medicines
* Concurrent treatment with an investigational agent within 28 days prior to the administration of paclitaxel and/or lapatinib
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to paclitaxel, including polyethoxylated castor oil, alcohol, or lapatinib or their excipients
* Anamnesis or diagnosis of pulmonary disorder, such as interstitial pneumonia, pulmonary fibrosis or serious hypoxia
* Gastrectomy surgery if Pilot Part of the study determines that partial gastrectomy (pylorus spared) or total/partial gastrectomy (pylorus removed) has a significant negative impact upon lapatinib PK and safety profile
* Known history of use of any EGFR agent (except Trastuzumab)
* Prior gastric cancer treatment which included a taxane.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) in the Pilot Part of the Study
timeFrame: 28 days
measure: Overall Survival (OS) in the Randomized Part of the Study
timeFrame: From randomization until death due to any cause (up to 42.58 months)
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study
timeFrame: Days 8 and 14
measure: Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study
timeFrame: Days 8 and 14
measure: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study
timeFrame: Days 8 and 14
measure: Cmax of Paclitaxel in the Pilot Part of the Study
timeFrame: Days 1 and 8
measure: Tmax of Paclitaxel in the Pilot Part of the Study
timeFrame: Days 1 and 8
measure: AUC(0-24) of Paclitaxel in the Pilot Part of the Study
timeFrame: Days 1 and 8
measure: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study
timeFrame: Days 1 and 8
measure: Half-life of Paclitaxel in the Pilot Part of the Study
timeFrame: Days 1 and 8
measure: Clearance of Paclitaxel in the Pilot Part of the Study
timeFrame: Days 1 and 8
measure: Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study
timeFrame: Days 1 and 8
measure: Progression-free Survival (PFS) in the Randomized Part of the Study
timeFrame: From randomization until disease progression or death due to any cause (up to 42.35 months)
measure: Time to Progression in the Randomized Part of the Study
timeFrame: From randomization until disease progression or death due to disease (up to 42.35 months )
measure: Percentage of Participants With Overall Response in the Randomized Part of the Study
timeFrame: From randomization up to 5.62 months
measure: Number of Participants With the Indicated Time to Response in the Randomized Part of the Study
timeFrame: up to 5.62 months
measure: Duration of Response in the Randomized Part of the Study
timeFrame: up to 18.27 months
measure: Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study
timeFrame: From the first dose of investigational product to 30 days after the last dose (up to 110.3 weeks in the Randomized part)
measure: Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QOL Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Role Functioning Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Social Functioning Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Fatigue Symptom Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Symptom Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Pain Symptom Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Dyspnea Symptom Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Insomnia Symptom Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Appetite Loss Symptom Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Constipation Symptom Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Diarrhea Symptom Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Symptom Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-STO22 Dysphagia Scale Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-STO22 Pain Scale Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-STO22 Reflux Symptoms Scale Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-STO22 Eating Restrictions Scale Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-STO22 Anxiety Scale Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-STO22 Dry Mouth Scale Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-STO22 Taste Scale Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-STO22 Body Image Scale Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Change From Baseline in the EORTC QLQ-STO22 Hair Loss Scale Score at the End of Therapy in the Randomized Part of the Study
timeFrame: Baseline and end of therapy (up to 42.58 months)
measure: Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study
timeFrame: Pretreatment
measure: Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study
timeFrame: Pretreatment
measure: Number of Participants With Mutations That May Correlate With Response and Toxicity to Lapatinib
timeFrame: Pretreatment
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Hwasun
country: Korea, Republic of
facility: GSK Investigational Site
city: Seongnam-si Gyeonggi-do
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: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: Niaosong Township, Kaohsiung
country: Taiwan
facility: GSK Investigational Site
city: Tainan County
country: Taiwan
facility: GSK Investigational Site
city: Tainan
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Tau-Yuan County
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: