Clinical trial NCT01450696: 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
Official title: A Randomized, Open Label, Multicenter Phase IIIb Study Comparing Two Trastuzumab Dosing Regimens, Each in Combination With Cisplatin/Capecitabine Chemotherapy, as First-Line Therapy in Patients With HER2-Positive Metastatic Gastric or Gastro-Esophageal Junction Adenocarcinoma Who Have Not Received Prior Treatment for Metastatic Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Gastric Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-10-12
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants Who Died - FAS
timeFrame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
measure: Overall Survival - FAS
timeFrame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Secondary outcomes:
measure: Percentage of Participants Who Died - Per Protocol Set (PPS)
timeFrame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
measure: Overall Survival - PPS
timeFrame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
measure: Percentage of Participants With Disease Progression or Death - PPS
timeFrame: 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)
measure: Progression-Free Survival - PPS
timeFrame: 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)
measure: Percentage of Participants With Objective Response - PPS
timeFrame: 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)
measure: Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS
timeFrame: Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days)
measure: Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS
timeFrame: Pre-dose (0 minutes) and within 15 minutes after end of 2-hour Herceptin infusion on Day 1 of Cycle 1 (cycle length = 21 days)
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Whittier
country: United States
state: California
city: Whittier
country: United States
state: California
city: Goshen
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: New York
country: United States
state: New York
city: Portland
country: United States
state: Oregon
city: Charleston
country: United States
state: South Carolina
city: Port Macquarie
country: Australia
state: New South Wales
city: Wahroonga
country: Australia
state: New South Wales
city: Woodville South
country: Australia
state: South Australia
city: Murdoch
country: Australia
state: Western Australia
city: Banja Luka
country: Bosnia and Herzegovina
city: Sarajewo
country: Bosnia and Herzegovina
city: Rio de Janeiro
country: Brazil
state: RJ
city: Porto Alegre
country: Brazil
state: RS
city: Barretos
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Sorocaba
country: Brazil
state: SP
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Viña del Mar
country: Chile
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Changchun
country: China
city: Changsha
country: China
city: Changzhou
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Nanjing
country: China
city: Shanghai
country: China
city: Wuhan
country: China
city: Zhengzhou
country: China
city: Brno
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Praha 8
country: Czech Republic
city: Berlin
country: Germany
city: Frankfurt
country: Germany
city: Mannheim
country: Germany
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Pecs
country: Hungary
city: Szolnok
country: Hungary
city: Szombathely
country: Hungary
city: Veszprem
country: Hungary
city: Catanzaro
country: Italy
state: Calabria
city: Napoli
country: Italy
state: Campania
city: Bologna
country: Italy
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
state: Emilia-Romagna
city: Udine
country: Italy
state: Friuli-Venezia Giulia
city: Milano
country: Italy
state: Lombardia
city: Ancona
country: Italy
state: Marche
city: Florence
country: Italy
state: Toscana
city: Pisa
country: Italy
state: Toscana
city: Bundang City
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Distrito Federal
country: Mexico
city: Mexico City
country: Mexico
city: Monterrey
country: Mexico
city: Oaxaca
country: Mexico
city: Auckland
country: New Zealand
city: Panama
country: Panama
city: Arequipa
country: Peru
city: Arequipa
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Trujillo
country: Peru
city: Manila
country: Philippines
city: Pasig City
country: Philippines
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Warsaw
country: Poland
city: Wieliszew
country: Poland
city: Porto
country: Portugal
city: Ivanovo
country: Russian Federation
city: Omsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Tula
country: Russian Federation
city: Belgrade
country: Serbia
city: Nis
country: Serbia
city: Sremska Kamenica
country: Serbia
city: Bloemfontein
country: South Africa
city: Cape Town
country: South Africa
city: Johannesburg
country: South Africa
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Adana
country: Turkey
city: Gaziantep
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Izmir
country: Turkey
city: Malatya
country: Turkey
city: Sıhhiye, ANKARA
country: Turkey
city: Cherkassy
country: Ukraine
city: Chernivtsi
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kiev
country: Ukraine
city: Lvov
country: Ukraine
city: Denbighshire
country: United Kingdom
city: Leicester
country: United Kingdom
city: Southampton
country: United Kingdom
city: Wolverhampton
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: