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

Novartis

Status and phase: Completed; Phase 3

Conditions: Neoplasms, Gastrointestinal Tract

Treatments: Drug: Oxaliplatin; Drug: Capecitabine; Drug: Placebo; Drug: Lapatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT00680901

2007-005725-29 (EudraCT Number)

CLAP016C2301 (Other Identifier)

EGF110656

Details and patient eligibility

About

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.

Enrollment: 545 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key inclusion criteria:

• Histologically confirmed gastric adenocarcinoma or adenocarcinoma of the esophagus or gastro-esophageal junction.

• Gastric cancer that is unresectable due to locally advanced (defined as stage IV: T4N1-3 or TanyN3), metastatic, or locally recurrent disease; Esophageal cancer that is unresectable due to locally advanced (T3N1 or T4Nany), metastatic or locally recurrent disease.

• Measurable or non-measurable, but radiologically evaluable disease, according to RECIST.

• HER2 amplification by FISH assessed by the local or designated central laboratory; Subjects with unknown HER2 status were not eligible.

• Adequate organ function, as defined in the study protocol, assessed within 14 days prior randomization.

• Cardiac ejection fraction within institutional range of normal as measured by echocardiogram (ECHO).

• Prior/Concurrent Therapy:

  • At least 3 weeks following major surgery, such as gastrectomy, and were recovered from any related toxicity More than 5 years since prior chemotherapy for malignancy other than GC. At least 4 weeks since prior radiotherapy
  • More than 5 years since prior biologic or hormonal therapy or immunotherapy for malignancy other than gastric carcinoma.

Key exclusion criteria:

• Pregnant or lactating females at any time during the study.
• Known history of active CNS disease.
• Uncontrolled ascites.
• Concurrent anti-cancer therapy (chemotherapy, radiation therapy other than for pain relief, immunotherapy, biologic therapy, hormonal therapy or surgery) while taking investigational treatment.
• Gastric carcinoid, epidermoid, sarcomas, or squamous cell carcinoma.
• Prior palliative chemotherapy for the treatment of gastric cancer.
• Prior treatment with oxaliplatin-based neoadjuvant or adjuvant chemotherapy completed <12 months.
• Malabsorption syndrome or uncontrolled inflammatory gastrointestinal disease (such as Crohn's disease or ulcerative colitis).
• Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.
• Uncontrolled infection.
• History of other malignancy. However, subjects who were disease-free for 5 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, were eligible.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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545 participants in 2 patient groups, including a placebo group

CapeOx plus Lapatinib

Experimental group

Description:

CapeOx plus Lapatinib

Treatment:

Drug: Lapatinib

Drug: Capecitabine

Drug: Oxaliplatin

CapeOx plus Placebo

Placebo Comparator group

Description:

CapeOx plus Placebo

Treatment:

Drug: Capecitabine

Drug: Placebo

Drug: Oxaliplatin