A Study of Herceptin (Trastuzumab) in Combination With Cisplatin/Capecitabine Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastric or Gastro-Esophageal Junction Cancer (HELOISE)

Roche

Status and phase: Terminated; Phase 3

Conditions: Gastric Cancer

Treatments: Drug: Cisplatin; Drug: Capecitabine; Drug: Herceptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01450696

BO27798

2011-001526-19 (EudraCT Number)

Details and patient eligibility

About

This randomized, open-label, multicenter, international Phase IIIb study will compare the efficacy and safety of two Herceptin dosing regimens in combination with cisplatin/capecitabine chemotherapy in participants with HER2-positive metastatic gastric or gastro-esophageal junction adenocarcinoma. Participants who have not received prior treatment for metastatic disease will be randomized to receive Herceptin intravenously as either an 8-milligram per kilogram (mg/kg) loading dose followed by 6 mg/kg every 3 weeks (q3w) as standard of care or an 8-mg/kg loading dose followed by 10 mg/kg q3w until disease progression. Capecitabine will be administered for 6 cycles at a dose of 800 milligrams per meter-squared (mg/m^2) orally twice a day on Days 1 to 14 of each 3-week cycle, and cisplatin will be administered intravenously for 6 cycles at a dose of 80 mg/m^2 on Day 1 of each 3-week cycle. Herceptin will be continued until disease progression occurs.

Enrollment: 296 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with metastatic disease documented to involve at least liver or lung or both
• Measurable disease according to RECIST Version 1.1 or non-measurable evaluable disease
• At least 2 organs involved in metastatic gastric tumor (including at least lung or liver or both) in addition to the site of primary tumor, where metastasis in distant lymph nodes, peritoneal metastasis, and malignant pleural effusion may count as "organs" in this context
• HER2-positive primary or metastatic tumor as assessed by central laboratory
• Adequate renal function (creatinine clearance greater than equal to (≥) 45 milliliters per minute [mL/min])
• Eastern Cooperative Oncology Group (ECOG) performance status of 2

Exclusion criteria

• Previous chemotherapy for locally advanced or metastatic disease
• Prior gastrectomy (partial or total) for the underlying malignant disease under investigation
• Prior therapy with an anti-HER2 agent and/or platinum-based chemotherapeutic agent
• Residual relevant toxicity resulting from previous therapy
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (such as jejunostomy probe and gastric or jejunostomy tubes) which may impair the ability to administer or absorb capecitabine
• Current (significant or uncontrolled) gastrointestinal bleeding
• Other malignancy within the last 5 years, except for carcinoma in situ of the cervix and basal or squamous cell carcinoma of the skin
• History of documented congestive heart failure, angina pectoris requiring medication, electrocardiogram (ECG) evidence of transmural myocardial infraction, poorly controlled hypertension, clinically significant valvular heart disease, or high-risk uncontrollable arrhythmias
• Baseline left ventricular ejection fraction (LVEF) less than (<) 50%, documented by echocardiography, multiple-gated radionuclide angiography (MUGA) scan, or cardiac magnetic resonance imaging (MRI)
• Chronic or high-dose corticosteroid therapy
• History or clinical evidence of brain metastases
• Pregnant women
• Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, or HIV-seropositive

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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296 participants in 2 patient groups

Capecitabine + Cisplatin + Herceptin (6 mg/kg)

Active Comparator group

Description:

Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as a standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m\^2 intravenously q3w plus capecitabine 800 mg/m\^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Treatment:

Drug: Herceptin

Drug: Cisplatin

Drug: Capecitabine

Capecitabine + Cisplatin + Herceptin (10 mg/kg)

Experimental group

Description:

Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m\^2 intravenously q3w plus capecitabine 800 mg/m\^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Treatment:

Drug: Herceptin

Drug: Cisplatin

Drug: Capecitabine