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
Condition: Neoplasms, Gastrointestinal Tract
MeSH terms: Gastrointestinal Neoplasms; Digestive System Neoplasms
Intervention: Lapatinib; Placebo; Capecitabine; Oxaliplatin
Intervention description: 5 pills at 250mg each once daily; 5 pills once daily; 1700mg/m2/day in two daily doses; 130mg/m2 on day 1
Intervention MeSH terms: Capecitabine; Oxaliplatin; Lapatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 545.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: unresectable; HER2; TYVERB; ErbB2; TYKERB; capecitabine; CapeOx; gastric/esophageal cancer; GE junction; metastatic; lapatinib; oxaliplatin

Summary:

      This is an international multi-center trial that will enroll patients with locally advanced,
      unresectable, or metastatic gastric, esophageal, or gastro-esophageal junction cancer whose
      tumors have amplification of the ErbB2 (HER2) gene. The trial will investigate whether
      lapatinib, when added to the chemotherapy regimen, capecitabine plus oxaliplatin (CapeOx),
      extends the time to progression and overall survival. Tumor ErbB2 (HER2) status must be known
      before trial entry. CapeOx is administered to all patients, and patients will be randomly
      assigned to receive either lapatinib or placebo.
    

Eligibility criteria:

        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