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

NCT ID: NCT01450696

Last Updated: 2016-11-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 296 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2015-08-31

Brief Summary

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.

Conditions

Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Capecitabine + Cisplatin + Herceptin (6 mg/kg)

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).

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

Capecitabine will be administered at a dose of 800 mg/m\^2 orally twice daily for 14 days q3w for up to 6 cycles (Cycles 1 to 6).

Cisplatin

Intervention Type: DRUG

Cisplatin will be administered at a dose of 80 mg/m\^2 intravenously q3w on Day 1 of each 3-week cycle for up to 6 cycles (Cycles 1 to 6).

Herceptin

Intervention Type: DRUG

Herceptin will be administered at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 or 10 mg/kg (depending upon treatment assignment) q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Capecitabine + Cisplatin + Herceptin (10 mg/kg)

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).

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

Capecitabine will be administered at a dose of 800 mg/m\^2 orally twice daily for 14 days q3w for up to 6 cycles (Cycles 1 to 6).

Cisplatin

Intervention Type: DRUG

Cisplatin will be administered at a dose of 80 mg/m\^2 intravenously q3w on Day 1 of each 3-week cycle for up to 6 cycles (Cycles 1 to 6).

Herceptin

Intervention Type: DRUG

Herceptin will be administered at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 or 10 mg/kg (depending upon treatment assignment) q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Interventions

Capecitabine

Capecitabine will be administered at a dose of 800 mg/m\^2 orally twice daily for 14 days q3w for up to 6 cycles (Cycles 1 to 6).

Intervention Type: DRUG

Cisplatin

Cisplatin will be administered at a dose of 80 mg/m\^2 intravenously q3w on Day 1 of each 3-week cycle for up to 6 cycles (Cycles 1 to 6).

Intervention Type: DRUG

Herceptin

Herceptin will be administered at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 or 10 mg/kg (depending upon treatment assignment) q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Intervention Type: DRUG

Other Intervention Names

Trastuzumab

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

La Jolla, California, United States

Los Angeles, California, United States

Whittier, California, United States

Whittier, California, United States

Goshen, Indiana, United States

Wichita, Kansas, United States

New York, New York, United States

Portland, Oregon, United States

Charleston, South Carolina, United States

Port Macquarie, New South Wales, Australia

Wahroonga, New South Wales, Australia

Woodville South, South Australia, Australia

Murdoch, Western Australia, Australia

Banja Luka, , Bosnia and Herzegovina

Sarajevo, , Bosnia and Herzegovina

Rio de Janeiro, Rio de Janeiro, Brazil

Porto Alegre, Rio Grande do Sul, Brazil

Barretos, São Paulo, Brazil

São Paulo, São Paulo, Brazil

Sorocaba, São Paulo, Brazil

Santiago, , Chile

Santiago, , Chile

Viña del Mar, , Chile

Beijing, , China

Beijing, , China

Beijing, , China

Beijing, , China

Changchun, , China

Changsha, , China

Changzhou, , China

Guangzhou, , China

Hangzhou, , China

Nanjing, , China

Shanghai, , China

Wuhan, , China

Zhengzhou, , China

Brno, , Czechia

Olomouc, , Czechia

Prague, , Czechia

Prague, , Czechia

Berlin, , Germany

Frankfurt, , Germany

Mannheim, , Germany

Budapest, , Hungary

Budapest, , Hungary

Pécs, , Hungary

Szolnok, , Hungary

Szombathely, , Hungary

Veszprém, , Hungary

Catanzaro, Calabria, Italy

Napoli, Campania, Italy

Bologna, Emilia-Romagna, Italy

Reggio Emilia, Emilia-Romagna, Italy

Udine, Friuli Venezia Giulia, Italy

Milan, Lombardy, Italy

Ancona, The Marches, Italy

Florence, Tuscany, Italy

Pisa, Tuscany, Italy

Distrito Federal, , Mexico

Mexico City, , Mexico

Monterrey, , Mexico

Oaxaca City, , Mexico

Auckland, , New Zealand

Panama City, , Panama

Arequipa, , Peru

Arequipa, , Peru

Lima, , Peru

Lima, , Peru

Lima, , Peru

Lima, , Peru

Trujillo, , Peru

Manila, , Philippines

Pasig, , Philippines

Krakow, , Poland

Lublin, , Poland

Warsaw, , Poland

Wieliszew, , Poland

Porto, , Portugal

Ivanovo, , Russia

Omsk, , Russia

Ryazan, , Russia

Saint Petersburg, , Russia

Stavropol, , Russia

Tula, , Russia

Belgrade, , Serbia

Kamenitz, , Serbia

Niš, , Serbia

Bloemfontein, , South Africa

Cape Town, , South Africa

Johannesburg, , South Africa

Bundang City, , South Korea

Incheon, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Barcelona, Barcelona, Spain

Barcelona, Barcelona, Spain

Madrid, Madrid, Spain

Adana, , Turkey (Türkiye)

Gaziantep, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Malatya, , Turkey (Türkiye)

Sıhhiye, Ankara, , Turkey (Türkiye)

Cherkassy, , Ukraine

Chernivtsi, , Ukraine

Dnipropetrovsk, , Ukraine

Donetsk, , Ukraine

Kiev, , Ukraine

Lviv, , Ukraine

Denbighshire, , United Kingdom

Leicester, , United Kingdom

Southampton, , United Kingdom

Wolverhampton, , United Kingdom

Countries

Costa Rica; India; Romania; United States; Australia; Bosnia and Herzegovina; Brazil; Chile; China; Czechia; Germany; Hungary; Italy; Mexico; New Zealand; Panama; Peru; Philippines; Poland; Portugal; Russia; Serbia; South Africa; South Korea; Spain; Turkey (Türkiye); Ukraine; United Kingdom

Other Identifiers

2011-001526-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO27798

Identifier Type: -

Identifier Source: org_study_id