Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Lapatinib

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

6 pills of lapatinib at 250 mg each once daily and infusion of paclitaxel at 80 mglm2 weekly

Infusion of paclitaxel at 80 mglm2 weekly

GSK Clinical Trials

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.

Lapatinib in Combination With Weekly Paclitaxel in Patients With ErbB2 Amplified Advanced Gastric Cancer

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

DLTs consisted of only drug-related toxicities (neurologic and non-neurologic DLTs). A neurologic DLT was defined as grade 3/4 clinically significant peripheral motor and/or sensitive neuropathy. Non-neurologic DLTs mainly included the following: grade 3/4 clinically significant non-hematological toxicity (except nausea), grade 4 neutropenia lasting \>=7 days, thrombocytopenia (\<=25000 cells per cubic millimeter), inability to begin next treatment within 2 weeks of scheduled dosing due to unresolved toxicity, treatment delay (due to toxicity) of \>5 days, for Days 8 or 15 of weekly paclitaxel.

OS was defined as the time from randomization until death due to any cause. For participants who did not die, time to death was censored at the time of last contact. For censored participants, time to death was defined as the time from randomization to the time of last contact.

Pharmacokinetic (PK) samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14.

PK samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14.

PK samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14. AUC is defined as the area under the lapatinib concentration-time curve as a measure of drug exposure. AUC(0-24) is area under the plasma concentration-time curve from time 0 to 24 hours after oral adminisation.

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8.

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. AUC is defined as the area under the paclitaxel concentration-time curve as a measure of drug exposure. AUC(0-24) is area under the plasma concentration-time curve from the start of infusion (time 0) to 24 hours after the start of the infusion.

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. AUC is defined as the area under the paclitaxel concentration-time curve as a measure of drug exposure. AUC(0-inf) is area under the plasma concentration-time curve from the start of infusion (time 0) extrapolated to infinity.

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Half-life is defined as the time required for the amount of the drug in the plasma to decrease by half.

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Clearance is defined as the clearance of drug from plasma, which is defined as the volume of plasma from which drug is removed per unit time.

PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Vss is the volume of distribution at steady state of paclitaxel.

PFS was defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0, PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.

Time to progression was defined as the time from randomization until the earliest date of disease progression or death due to disease. Per RECIST, version 1.0, PD is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.

Overall response was defined as the percentage of participants achieving either complete response (CR) or partial response (PR). Per RECIST, version 1.0, CR was defined as the disappearance of all target lesions, and PR was defined as a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Time to response was defined as the time from randomization to CR (the disappearance of all target lesions) or PR (a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD). For participants who did not achieve a CR or PR, time to response was censored at the last assessment prior to other cancer therapies. For censored participants, time to response was defined as the time from randomization to the time of the last assessment prior to the administation of other cancer therapies.

Duration of response was defined as the time from the first documented evidence of CR (the disappearance of all target lesions) or PR (a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD) until the first documented sign of disease progression (at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions) or death due to any cause, if sooner.

The Common Terminology Criteria for Advere Events (CTCAE) is a descriptive terminology that can be used for AE reporting. Grade (G) refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade (G) refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE.

The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.

The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.

EGFR protein expression on the surface of cells in gastric cancer tissue samples was measured using a moncolonal antibody specific for the extracellular region of EGFR, and the degree of membrane staining was evaluated. 3+ indicates positive EGFR expression; \<3+ indicates negative EGFR expression.

HER2 protein expression on the surface of cells in gastric cancer tissue samples was measured using a monoclonal antibody specific for the extracellulr region of HER2, and the degree of membrane staining was evaulated. The immunohistochemistry test gives a score of 0 to 3+ and measures the amount of HER2 receptor protein on the surface of cells in a gastric cancer tissue sample. Score of 0 to 1+, "HER2 negative"; score of 2+, "borderline"; score of 3+, "HER2 positive."

An inadequate number of tissue samples were obtained; thus, analysis could not be performed.

GlaxoSmithKline

SAEs and non-serious AEs were collected in members of the Safety Population in both the Pilot part and the Randomized part . For the Pilot part, MedDRA 12.1 was used; for the Randomized part, MedDRa 15.1 was used.

In the Pilot part, participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).

Lapatinib Plus Paclitaxel in Non-gastrectomy Participants

In the Pilot part, participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.

Lapatinib Plus Paclitaxel in Gastrectomy Participants

Participants received 1500 mg of oral lapatinib once daily throughout the study duration. Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).

Lapatinib Plus Paclitaxel in Randomized Part

Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle).

Paclitaxel Alone in Randomized Part

Total

Age Continuous

Sex: Female, Male

Asian - Japanese Heritage

Asian - East Asian Heritage

Asian - South East Asian Heritage

Race/Ethnicity, Customized

GSK Response Center

Participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2).

Participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2.

Safety Population (Pilot part): all participants who received at least one dose of investigational product in the Pilot part of the study

Number of Participants With Dose Limiting Toxicities (DLTs) in the Pilot Part of the Study

Lapatinib Plus Paclitaxel

Paclitaxel Alone

Intent-to-Treat Population: all participants who were randomized to study treatment, regardless of whether they actually received study medication

Overall Survival (OS) in the Randomized Part of the Study

Day 8

Day 14

PK Parameter Population: all participants for whom the PK parameter could be estimated

Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study

Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study

Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study

Day 1

Cmax of Paclitaxel in the Pilot Part of the Study

Tmax of Paclitaxel in the Pilot Part of the Study

AUC(0-24) of Paclitaxel in the Pilot Part of the Study

Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study

Half-life of Paclitaxel in the Pilot Part of the Study

Clearance of Paclitaxel in the Pilot Part of the Study

Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study

ITT Population. For participants whose disease did not progress or who did not die, PFS was censored at the time of the last independently assessed radiological scan preceding the initiation of any alternate anti-cancer therapy.

Progression-free Survival (PFS) in the Randomized Part of the Study

Time to Progression in the Randomized Part of the Study

Percentage of Participants With Overall Response in the Randomized Part of the Study

Weeks 1-8

Weeks >8 - 16

Weeks >16 - 24

Weeks >24 - 32

ITT Population. Only those participants achieving a CR or PR were assessed.

Number of Participants With the Indicated Time to Response in the Randomized Part of the Study

Duration of Response in the Randomized Part of the Study

Diarrhoea, Grade 3

Diarrhoea, Grade 4

Nausea, Grade 3

Nausea, Grade 4

Vomiting, Grade 3

Vomiting, Grade 4

Stomatitis, Grade 3

Stomatitis, Grade 4

Constipation, Grade 3

Constipation, Grade 4

Abdominal pain, Grade 3

Abdominal pain, Grade 4

Neutropenia, Grade 3

Neutropenia, Grade 4

Leukopenia, Grade 3

Leukopenia, Grade 4

Anaemia, Grade 3

Anaemia, Grade 4

Lymphopenia, Grade 3

Lymphopenia, Grade 4

Alopecia, Grade 3

Alopecia, Grade 4

Rash, Grade 3

Rash, Grade 4

Pruritus, Grade 3

Pruritus, Grade 4

Fatigue, Grade 3

Fatigue, Grade 4

Pyrexia, Grade 3

Pyrexia, Grade 4

Asthenia, Grade 3

Asthenia, Grade 4

Weight decreased, Grade 3

Weight decreased, Grade 4

White blood cell count decreased, Grade 3

White blood cell count decreased, Grade 4

Neutrophil count decreased, Grade 3

Neutrophil count decreased, Grade 4

Haemoglobin decreased, Grade 3

Haemoglobin decreased, Grade (G) 4

Aspartate aminotransferase increased, G 3

Aspartate aminotransferase increased, G 4

Alanine aminotransferase increased, G 3

Alanine aminotransferase increased, G 4

Peripheral sensory neuropathy, G 3

Peripheral sensory neuropathy, G 4

Neuropathy peripheral, Grade 3

Neuropathy peripheral, Grade 4

Decreased appetite, Grade 3

Decreased appetite, Grade 4

Myalgia, Grade 3

Myalgia, Grade 4

Arthralgia, Grade 3

Arthralgia, Grade 4

Back pain, Grade 3

Back pain, Grade 4

Safety Population: all participants who were randomized and took at least one dose of study medication

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

ITT Population. Only those participants who contributed data were analyzed.

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

Change From Baseline in the EORTC QLQ-C30 Physical Functioning Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Role Functioning Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Social Functioning Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Fatigue Symptom Score at the End of Therapy in the Randomized Part of the Study

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

Change From Baseline in the EORTC QLQ-C30 Pain Symptom Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Dyspnea Symptom Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Insomnia Symptom Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Appetite Loss Symptom Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Constipation Symptom Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Diarrhea Symptom Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Symptom Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-STO22 Dysphagia Scale Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-STO22 Pain Scale Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-STO22 Reflux Symptoms Scale Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-STO22 Eating Restrictions Scale Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-STO22 Anxiety Scale Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-STO22 Dry Mouth Scale Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-STO22 Taste Scale Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-STO22 Body Image Scale Score at the End of Therapy in the Randomized Part of the Study

Change From Baseline in the EORTC QLQ-STO22 Hair Loss Scale Score at the End of Therapy in the Randomized Part of the Study

ITT Population. Only those participants for whom immunohistochemistry testing was conducted were analyzed.

Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study

0/1+

Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study

Number of Participants With Mutations That May Correlate With Response and Toxicity to Lapatinib

Participants with partial gastrectomy (which includes preservation of the pylorus) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2. Partial gastrectomy (pylorus preserved) is very rare population in Japan. As a result, no such participants were recruited into this cohort.

Spots Global Cancer Trial Database for Lapatinib in Combination With Weekly Paclitaxel in Patients With ErbB2 Amplified Advanced Gastric Cancer

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Study Description

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