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

Phase 3TerminatedNCT01450696

Hoffmann-La Roche296 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

296

Conditions

Gastric Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (117)

Unnamed facility

La Jolla, California, United States

Unnamed facility

Los Angeles, California, United States

Unnamed facility

Whittier, California, United States

Unnamed facility

Whittier, California, United States

Unnamed facility

Goshen, Indiana, United States

Unnamed facility

Outcomes

Primary Outcomes

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.

Time frame: 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.

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

Secondary Outcomes

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

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

Time frame: 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

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 PPS using the Kaplan-Meier approach. The 95% CI for median was computed using the method of Brookmeyer and Crowley.

Time frame: 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

Disease progression was defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of ≥5 millimeters (mm). The percentage of participants who died or experienced disease progression as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.

Time frame: 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

Progression-free survival was defined as the time between the day of randomization and the date of first documentation of disease progression or date of death, whichever occurred first, measured following RECIST Version 1.1 criteria. Disease progression was defined as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of ≥5 mm. The 95% CI for median was computed using the method of Brookmeyer and Crowley.

Time frame: 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

Objective response was defined as the occurrence of either a complete response (CR) or partial response (PR) as determined by RECIST Version 1.1 based on investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) were required to have reduction in short axis to \<10 mm. PR was defined as a ≥30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. The 95% CI was constructed using Blyth-Still-Casella method.

Time frame: 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)

Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS

Cmin samples were obtained in all participants randomized to receive Herceptin (FAS). The observed Cmin was recorded, averaged among all participants, and expressed in μg/mL.

Time frame: Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days)

Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS

Trastuzumab serum concentration samples were obtained in all participants randomized to receive Herceptin (FAS). The observed concentration values were recorded, averaged among all participants, and expressed in μg/mL.

Time frame: 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)