LOGiC - Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib

Phase 3

Completed

Conditions: Neoplasms, Gastrointestinal Tract

Interventions: Drug: Lapatinib
Drug: Placebo
Drug: Capecitabine
Drug: Oxaliplatin

Registration Number: NCT00680901

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This was an international multi-center trial that enrolled patients with locally advanced, unresectable, or metastatic gastric, esophageal, or gastro-esophageal junction cancer whose tumors had amplification of the ErbB2 (HER2) gene. The trial investigated whether lapatinib, when added to the chemotherapy regimen, capecitabine plus oxaliplatin (CapeOx), extended the time to progression and overall survival. Tumor ErbB2 (HER2) status had to be known before trial entry. CapeOx was administered to all patients, and patients were randomly assigned to receive either lapatinib or placebo.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 545

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CapeOx plus Lapatinib	Lapatinib	CapeOx plus Lapatinib
CapeOx plus Lapatinib	Capecitabine	CapeOx plus Lapatinib
CapeOx plus Lapatinib	Oxaliplatin	CapeOx plus Lapatinib
CapeOx plus Placebo	Placebo	CapeOx plus Placebo
CapeOx plus Placebo	Capecitabine	CapeOx plus Placebo
CapeOx plus Placebo	Oxaliplatin	CapeOx plus Placebo

Primary Outcome Measures

Name	Time	Method
Overall Survival at the Time of Primary Analysis	From date of randomization till death due to any cause, assessed up the cut-off date for Primary Analysis (24-Sep-2012) (average of 4 years)	Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.
Overall Survival in All Randomized Participants at the Time of Primary Analysis	From date of randomization till death due to any cause, assessed up the cut-off date for Primary Analysis (24-Sep-2012) (average of 4 years)	Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.

Secondary Outcome Measures

Name	Time	Method
Overall Survival at the Time of Final Analysis	From date of randomization till death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.
Progression Free Survival (PFS)	From date of randomization till the earliest date of disease progression or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	Progression-Free Survival (PFS) was defined as the time from randomization to the earliest occurrence of disease progression or death from any cause. Per RECIST v1.0, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants with symptomatic progression, even without radiological confirmation, were also counted. Those who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Participants who received non-study anti-cancer therapies before progression were also censored.
Percentage of Participants With a Confirmed Complete Response (CR) or a Partial Response (PR)	From date of randomization till the date of the first documented response of CR or PR, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	A participant was considered a responder if they had achieved either a complete response (CR), defined as the disappearance of all target and non-target lesions, or a partial response (PR), defined as at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, as assessed by the investigator and confirmed by radiographic imaging within four weeks of the initial observation.
Percentage of Participants With Clinical Benefit (CB)	From date of randomization till date of disease progression (PD) or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	Clinical Benefit (CB) was defined as evidence of a complete response (CR), partial response (PR), or stable disease (SD). CR referred to the disappearance of all target and non-target lesions, PR to at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, and SD to neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression, based on the smallest sum of diameters recorded since treatment initiation. All assessments were made by the investigator.
Time to Response (TTR)	From date of randomization till the first documented evidence of confirmed CR or PR, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	Time to Response (TTR) was defined as the duration from randomization to the first documented evidence of either a complete response (CR) (the disappearance of all target and non-target lesions) or a partial response (PR) (at least a 30% reduction in the sum of the longest diameters of target lesions from baseline) as assessed by the investigator.
Duration of Response (DOR)	From the time of the first documented evidence of a confirmed CR or PR until the earliest date of disease progression or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	Duration of Response (DOR) was defined as the time from the first documented evidence of a complete response (CR) or partial response (PR) until the first recorded sign of disease progression or death from any cause. According to RECIST, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Those who received non-study anti-cancer therapies before progression were also censored.
Percentage of Participants With Any On-therapy Adverse Event (AE) and Serious Adverse Event (SAE)	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its causal relationship. This included any unfavorable or unintended sign (such as abnormal lab findings), symptom, or disease, whether new or worsened. A Serious Adverse Event (SAE) was defined as any such occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury.
Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its relationship to the product. This included any unfavorable or unintended sign (such as abnormal lab results), symptom, or disease, whether new or worsened. The severity of AEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity).
Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	A Serious Adverse Event (SAE) was defined as any such occurrence that resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury. The severity of SAEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity).
Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores	From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	The EORTC QLQ-C30 is a comprehensive questionnaire developed for assessing the quality of life of cancer patients across different aspects including function scales namely physical, role, cognitive, emotional and social; symptom scales such as fatigue, pain, nausea and vomiting; and a global scale pronouncing overall health status. Its scoring method involves a 4-point Likert scale (ranging from 1 'Not at all' to 4 'Very Much'). Domain scores are calculated by averaging the items within the respective domain and then linearly transforming the score to fit within a 0-100 scale to finalize the scores. In terms of interpretation, a high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Percentage of Participants With Worst-case On-therapy Chemistry Toxicities	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	The severity of chemistry parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening). Chemistry data included: Alanine aminotransferase (ALT), Albumin, Alkaline phosphatases (ALP), Aspartate aminotransferase (AST), Calcium (hypercalcemia), Calcium (hypocalcemia), Creatine Kinase (CK), Creatine, Glucose (hyperglycemia), Glucose (hypoglycemia), Magnesium (hypermagnesemia), Magnesium (hypomagnesemia), Potassium (hyperkalemia), Potassium (hypokalemia), Sodium (hypernatremia), Sodium (hyponatremia) and Total Bilirubin.
Percentage of Participants With Worst-case On-therapy Hematologic Toxicities	From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	The severity of hematologic parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening). Hematology data included: Hemoglobin, Platelet count, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) and White Blood Cell count.
Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale	From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	The QLQ-STO22 consists of 22 items divided into five subscales: dysphagia, pain, reflux, eating restrictions and anxiety, as well as single items addressing dry mouth, body image, taste, and hair loss. Each item is answered on a 4-point scale, ranging from 1 (not at all) to 4 (very much). Raw scores for each subscale or single item are calculated by averaging the scores of the individual items that make up the scale. These scores are then linearly transformed to range from 0 to 100. In terms of interpretation, a higher score indicates a worse quality of life concerning the specific symptoms assessed.
Mean Change From Baseline in Utility Score (Health Utility Index) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire	From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	The EQ-5D is a standardized instrument developed by the EuroQoL Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score. The Utility Score (Health Utility Index) is derived from the five dimensions of the EQ-5D descriptive system (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has levels indicating severity (e.g., 1 = no problems, 2 = some problems, 3 = extreme problems). These combinations form a health state, which is then converted into a single index value using a country-specific value set. In the UK-based value set, the possible EQ-5D index utility values range from -0.594 to 1.0, where: 1.0 = perfect health, 0 = death and \< 0 = health states considered worse than death.
Mean Change From Baseline in Thermometer Score (EQ VAS) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire	From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)	The EQ-5D is a standardized instrument developed by the EuroQol Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score. The Thermometer Score is a self-rated health score using a vertical visual analogue scale , where respondents rate their overall health on a scale from 0 (worst imaginable health) to 100 (best imaginable health).