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
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| ClinicalTrials.gov Identifier: NCT00680901 |
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Recruitment Status :
Active, not recruiting
First Posted : May 20, 2008
Results First Posted : October 29, 2013
Last Update Posted : April 3, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neoplasms, Gastrointestinal Tract | Drug: Lapatinib Drug: Placebo Drug: Capecitabine Drug: Oxaliplatin | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 545 participants |
| Allocation: | Randomized |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III Study for ErbB2 Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Junction Adenocarcinoma Treated With Capecitabine Plus Oxaliplatin With or Without Lapatinib |
| Actual Study Start Date : | June 4, 2008 |
| Actual Primary Completion Date : | September 24, 2012 |
| Estimated Study Completion Date : | August 22, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: CapeOx plus Lapatinib
CapeOx plus Lapatinib
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Drug: Lapatinib
5 pills at 250mg each once daily
Other Names:
Drug: Capecitabine 1700mg/m2/day in two daily doses Drug: Oxaliplatin 130mg/m2 on day 1 |
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Placebo Comparator: CapeOx plus Placebo
CapeOx plus Placebo
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Drug: Placebo
5 pills once daily Drug: Capecitabine 1700mg/m2/day in two daily doses Drug: Oxaliplatin 130mg/m2 on day 1 |
- Overall Survival [ Time Frame: From randomization until death due to any cause (average of 51 weeks) ]Overall Survival is defined as the time from randomization until death due to any cause. Participants who had not died were censored at the follow-up visit as either follow-up ended or follow-up ongoing.
- Overall Survival in All Randomized Participants [ Time Frame: From randomization until death due to any cause (average of 51 weeks) ]Overall Survival is defined as the time from randomization until death due to any cause. Participants who had not died were censored at the follow-up visit as either follow-up ended or follow-up ongoing.
- Progression Free Survival (PFS) [ Time Frame: From randomization until the earliest date of disease progression or death due to any cause (average of 30 weeks) ]PFS is defined as the interval between the date of randomization and 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 diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started or the appearance of >= 1 new lesion. Participants who did not have a radiological assessed PD but had symptomatic PD were also counted. Participants who had neither progressed nor died were censored at the follow-up visit as either follow-up ended or follow-up ongoing. Participants who received non-study anti-cancer therapies before disease progression were treated as censored.
- Number of Participants With a Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) [ Time Frame: From randomization until the date of the first documented response of CR or PR (average of 9 weeks) ]A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target and non-target lesions) or a PR (at least a 30% decrease in the sum of the longest diameters [LD] of target lesions, taking as a reference the Baseline sum LD) as assessed by the investigator (confirmed by radiographic imaging within 4 weeks from initial observations).
- Number of Participants With Clinical Benefit (CB) [ Time Frame: From randomization until disease progression (PD) or death due to any cause (average of 30 weeks) ]CB is defined as evidence of a CR (disappearance of all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD) at any time or stable disease (SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started) as assessed by the investigator.
- Time to Response (TTR) [ Time Frame: From Baseline (Day 1) until the first documented evidence of confirmed CR or PR (average of 9 weeks) ]TTR is defined as the time from randomization until the date of the first documented evidence of CR (the disappearance if all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking a reference the Baseline sum LD) as assessed by the investigator.
- Duration of Response (DOR) [ Time Frame: 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 (average of 36 weeks) ]DOR is defined as the time from the first documented evidence of a CR (the disappearance of all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD) until the first documented sign of PD or death due to any cause. Per RECIST, PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started or the appearance of >=1 new lesion. Participants who had neither progressed nor died were censored at the follow-up visit as either follow-up ended or follow-up ongoing. Participants who received non-study anti-cancer therapies before disease progression were treated as censored.
- Number of Participants With Any Non-serious Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) or Any Serious Adverse Event (SAE) [ Time Frame: From the first dose of study medication until 30 days after the last dose (average of 229 days) ]An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
- Number of Participants With Adverse Events of the Indicated Severity, Per the National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE) [ Time Frame: From the first dose of study medication until 30 days after the last dose (average of 229 days) ]An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. AE/SAE severity was graded according to NCI CTCAE, version 3.0: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.
- Mean Change in Scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) From Baseline to Week 36 [ Time Frame: From Baseline (Day1) to Week 36 ]The QLQ-C30, a self administered tool used to assess HROL, consists of 30 items that assesses 15 domains consisting of 5 functional scales (s.) (physical, role, emotional, cognitive, social) and nine symptom s. or single items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status or QOL s.. For the functional s. and symptom s. or single items, participants assessed using a 4-point s. (1=not at all; 2=a little; 3=quite a bit; 4=very much), whereas global health status or QOL was assessed using a 7-item Likert s., ranging from "poor" to "excellent." All s. and single-item scores ranged from 0 to 100. For the functional scores, a higher score indicated a better HRQOL, i.e. 0=worst HRQOL, 100=best HRQOL; for the symptom s. or single items , a higher score indicated a high level of symptoms and problems, i.e. 0=no symptoms, 100=most severe symptoms.
- Mean Change in Scores on the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) From Baseline to Week 36 [ Time Frame: From Baseline (Day1) to Week 36 ]The EORTC QLQ-STO22, the Gastric module of QLQ-C30, is a self administered tool use to assess HROOL of patients with gastric cancer. It consists of 22 items consisting of nine symptom scales or single items (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, taste, body image, hair loss) that were developed for participants with gastric cancer. For the symptom scales or single items, participants assessed using a 4-point scale (1=not at all; 2=a little; 3=quite a bit; 4=very much). All scales and single-item scores ranged from 0 to 100. For the symptom scales or single items, a higher score indicated a high level of symptoms and problems, i.e. 0=no symptoms, 100=most severe symptoms.
- Mean Change in Scores on the Questionnaire EuroQoL-5 Dimensions (EQ-5D) From Baseline to Week 36 [ Time Frame: From Baseline (Day1) to Week 36 ]The EQ-5D is a generic preference-based HROOL self administered tool comprising of a 5-dimensional health status measure (5D utility measure) and a visual analog rating scale feeling thermometer (T.). 5D utility measures mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. T. assesses participant's current health state. Each 5D utility question was responded to on a 3-point scale, indicating the level of impairment (1=no problem; 2=some or moderate problem(s); 3=unable, or extreme problems). The index utility values corresponding to the 243 health states were defined by the EuroQol classification and calculated based on country-specific regression coefficients. In the UK-based value set, the possible EQ-5D index utility values range from -0.594 to 1. The T. value ranges from 0 to 100. EQ-5D utility index score 0=death, 1=perfect health, -0.594 = worse than death. The T. score: 100=best imaginable health state, 0=worse imaginable health state.
- Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Clinical Chemistry Parameters [ Time Frame: From Baseline (Day 1) until 28 days after the last dose (average of 239 days) ]Data are summarized by NCI CTCAE, version 3.0 toxicity grades. Data are reported as the number of participants who had a Grade 3 (G3) or Grade 4 (G4) toxicity for the indicated clinical chemistry parameters: G3 indicates a severe toxicity, and G4 indicates a life-threatening toxicity. Clinical chemistry parameters included: Albumin, Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amino Transeferase (AST), Total Bilirubin (TB), Calcium (Hypercalcemia and Hypocalcemia), Creatine Kinase (CK), Creatinine, Glucose (Hyperglycemia [high] and Hypoglycemia [low]), Potassium (Hyperkalemia [high] and Hypokalemia [low]), Magnesium (Hypermagnesemia [high] and Hypomagnesemia [low]), and Sodium (Hypernatremia [high] and Hyponatremia [low]).
- Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Hematology Parameters [ Time Frame: From Baseline (Day 1) until 28 days after the last dose (average of 239 days) ]Data are summarized by NCI CTCAE, version 3.0 toxicity grades. Data are reported as the number of participants who had a Grade 3 (G3) or Grade 4 (G4) toxicity for indicated hematology parameters: G3 indicates a severe toxicity, and G4 indicates a life-threatening toxicity. Hematology parameter included: Hemoglobin (Hemo), Total Neutrophils (TN) Absolute, Platelet Count (PC), and White Blood Cell (WBC) Count.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Signed informed consent; Histologically confirmed gastric, esophageal, or gastro-esophageal junction adenocarcinoma; disease that is locally advanced (unresectable), metastatic, or locally recurrent disease; Measurable or non-measurable, but radiologically evaluable disease, according to RECIST; ErbB2 (HER2)positive; Age =18 years; ECOG Performance status = 2; Adequate organ function, including adequate hematologic, renal and liver function; Cardiac ejection fraction within institutional range of normal as measured by echocardiogram; Able to swallow and retain oral medications, and/or receive enteral medications via gastrectomy feeding tube; Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study; Prior gastric surgery is permitted if > 3 weeks prior and recovered; Prior chemotherapy for non-gastric malignancy if > than 5 years; Prior neoadjuvant and/or adjuvant chemotherapy for early stage gastric cancer if > 6 months since completion; At least 4 weeks since prior radiotherapy; Prior biologic, hormonal, or immunologic cancer treatment if > 5 years since treatment.
Exclusion Criteria:
Pregnant or lactating females; Known history of active CNS disease; Uncontrolled ascites; Concurrent anti-cancer therapy; Gastric carcinoid, epidermoid, sarcomas, or squamous cell carcinoma; Prior palliative chemotherapy for the treatment of gastric cancer; Prior treatment with oxaliplatin < 12 months; Malabsorption syndrome or uncontrolled inflammatory gastrointestinal disease; Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; Pre-existing grade = 2 motor or sensory neuropathy; Uncontrolled infection; Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical condition that would interfere with the subject''s safety; Active hepatic or biliary disease; History of other malignancy except if disease-free for 5 years, a history of completely resected non-melanoma skin cancer, or a successfully treated in situ carcinoma; Unresolved or unstable serious toxicity from prior administration of another investigational drug and/or prior cancer treatment; Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent; Known history of DPD deficiency; Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib, capecitabine, fluorouracil, platins or their excipients; Use of any investigational drug within 30 days prior randomization; Use of concurrent prohibited medications that would interact with study medications
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): NCT00680901
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| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT00680901 |
| Other Study ID Numbers: |
EGF110656 2007-005725-29 ( EudraCT Number ) CLAP016C2301 ( Other Identifier: Novartis ) |
| First Posted: | May 20, 2008 Key Record Dates |
| Results First Posted: | October 29, 2013 |
| Last Update Posted: | April 3, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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unresectable HER2 TYVERB ErbB2 TYKERB capecitabine |
CapeOx gastric/esophageal cancer GE junction metastatic lapatinib oxaliplatin |
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Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Capecitabine Oxaliplatin |
Lapatinib Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Tyrosine Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors |