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

NCT01450696 | Terminated Phase 3 Results

• 2 other identifiers: BO277982011-001526-19
• Study Type: interventional
• Target: 296
• Locations: 25 countries
• Sites: 117

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Died - FAS

  The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the FAS with available data.

  From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

• Overall Survival - FAS

  Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the FAS using the Kaplan-Meier approach. The 95 percent (%) confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.

  From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

Secondary Outcomes (7)

• Percentage of Participants Who Died - Per Protocol Set (PPS)

  From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

• Overall Survival - PPS

  From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

• Percentage of Participants With Disease Progression or Death - PPS

  From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)

• Progression-Free Survival - PPS

  From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)

• Percentage of Participants With Objective Response - PPS

  From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)

Study Arms (2)

Capecitabine + Cisplatin + Herceptin (6 mg/kg)

ACTIVE COMPARATOR

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).

Drug: Capecitabine; Drug: Cisplatin; Drug: Herceptin

Capecitabine + Cisplatin + Herceptin (10 mg/kg)

EXPERIMENTAL

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).

Drug: Capecitabine; Drug: Cisplatin; Drug: Herceptin

Interventions

Capecitabine 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).

Capecitabine + Cisplatin + Herceptin (10 mg/kg); Capecitabine + Cisplatin + Herceptin (6 mg/kg)

Cisplatin 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).

Capecitabine + Cisplatin + Herceptin (10 mg/kg); Capecitabine + Cisplatin + Herceptin (6 mg/kg)

Herceptin 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.

Also known as: Trastuzumab

Capecitabine + Cisplatin + Herceptin (10 mg/kg); Capecitabine + Cisplatin + Herceptin (6 mg/kg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (117)

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La Jolla, California, 92093, United States

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Los Angeles, California, 90033, United States

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Whittier, California, 90603, United States

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Whittier, California, 90606, United States

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Goshen, Indiana, 46526, United States

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Wichita, Kansas, 67214-3728, United States

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New York, New York, 10065, United States

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Portland, Oregon, 97239, United States

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Charleston, South Carolina, 29425, United States

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Port Macquarie, New South Wales, 2444, Australia

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Wahroonga, New South Wales, 2076, Australia

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Woodville South, South Australia, 5011, Australia

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Murdoch, Western Australia, 6150, Australia

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Banja Luka, 78000, Bosnia and Herzegovina

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Sarajevo, 71000, Bosnia and Herzegovina

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Rio de Janeiro, Rio de Janeiro, 20560-120, Brazil

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Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

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Barretos, São Paulo, 14784-400, Brazil

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São Paulo, São Paulo, 01246-000, Brazil

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Sorocaba, São Paulo, 18030-245, Brazil

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Santiago, 7500921, Chile

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Santiago, 8380456, Chile

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Viña del Mar, 2520612, Chile

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Beijing, 100050, China

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Beijing, 100071, China

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Beijing, 100142, China

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Beijing, 100853, China

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Changchun, 130012, China

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Changsha, 410006, China

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Changzhou, 213003, China

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Guangzhou, 510060, China

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Hangzhou, 310016, China

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Nanjing, China

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Shanghai, 200032, China

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Wuhan, 430030, China

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Zhengzhou, 450008, China

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Brno, 656 53, Czechia

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Olomouc, 775 20, Czechia

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Prague, 128 08, Czechia

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Prague, 180 81, Czechia

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Berlin, 10117, Germany

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Frankfurt, 60488, Germany

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Mannheim, 68167, Germany

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Budapest, 1097, Hungary

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Budapest, 1145, Hungary

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Pécs, 7623, Hungary

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Szolnok, 5004, Hungary

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Szombathely, 9700, Hungary

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Veszprém, 8200, Hungary

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Catanzaro, Calabria, 88100, Italy

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Napoli, Campania, 80131, Italy

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Bologna, Emilia-Romagna, 40138, Italy

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Reggio Emilia, Emilia-Romagna, 42100, Italy

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Udine, Friuli Venezia Giulia, 33100, Italy

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Milan, Lombardy, 20133, Italy

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Ancona, The Marches, 60121, Italy

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Florence, Tuscany, 50124, Italy

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Pisa, Tuscany, 56100, Italy

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Distrito Federal, 14080, Mexico

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Mexico City, 06760, Mexico

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Monterrey, 64020, Mexico

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Oaxaca City, 68000, Mexico

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Auckland, 1023, New Zealand

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Panama City, 0834-02723, Panama

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Arequipa, 04001, Peru

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Arequipa, 5154, Peru

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Lima, 1, Peru

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Lima, 34, Peru

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Lima, Lima 1, Peru

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Lima, Lima 41, Peru

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Trujillo, 13011, Peru

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Manila, 1000, Philippines

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Pasig, 1605, Philippines

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Krakow, 31-501, Poland

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Lublin, 20-090, Poland

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Warsaw, 00-973, Poland

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Wieliszew, 05-135, Poland

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Porto, 4200-072, Portugal

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Ivanovo, 153040, Russia

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Omsk, 644013, Russia

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Ryazan, 390011, Russia

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Saint Petersburg, Russia

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Stavropol, 355045, Russia

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Tula, 300053, Russia

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Belgrade, 11000, Serbia

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Kamenitz, 21204, Serbia

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Niš, 18000, Serbia

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Bloemfontein, 9300, South Africa

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Cape Town, 7506, South Africa

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Johannesburg, 2193, South Africa

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Bundang City, 463-802, South Korea

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Incheon, 405-760, South Korea

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Seoul, 03722, South Korea

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Seoul, 06351, South Korea

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Seoul, 110-744, South Korea

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Seoul, 130-872, South Korea

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Seoul, 135-720, South Korea

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Barcelona, Barcelona, 08035, Spain

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Barcelona, Barcelona, 08041, Spain

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Madrid, Madrid, 28046, Spain

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Adana, 01250, Turkey (Türkiye)

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Gaziantep, 27100, Turkey (Türkiye)

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Istanbul, 34890, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Malatya, 44280, Turkey (Türkiye)

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Sıhhiye, Ankara, 06100, Turkey (Türkiye)

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Cherkassy, 18009, Ukraine

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Chernivtsi, 58013, Ukraine

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Dnipropetrovsk, 49102, Ukraine

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Donetsk, 83092, Ukraine

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Kiev, 03115, Ukraine

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Lviv, 79031, Ukraine

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Denbighshire, LL185UJ, United Kingdom

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Leicester, LE1 5WW, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Wolverhampton, WV10 0QP, United Kingdom

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MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Capecitabine; Cisplatin; Trastuzumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Trial was stopped for futility based on pre-planned interim analysis results.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2011
• First Posted: October 12, 2011
• Study Start: December 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: August 1, 2015
• Last Updated: November 28, 2016
• Results First Posted: November 28, 2016

Record last verified: 2016-10

Locations

UA (6); IT (9); PE (7); PH (2); PA (1); GB (4); BO (2); CN (13); ES (3); PT (1); PL (4); KR (7); HU (6); BR (5); CL (3); US (9); SE (3); AU (4); TU (7); CZ (4); RU (6); ZA (3); DE (3); ME (4); NZ (1)