A Study of the Combination of Oxaliplatin, Capecitabine, and Trastuzumab With Chemoradiotherapy in the Adjuvant Setting in Operated Participants With Human Epidermal Growth Factor Receptor-2 Positive (HER2+) Gastric or Gastroesophageal Junction Cancer

Study Overview
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Brief Summary
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This single-arm, open-label study will evaluate the safety and efficacy of the combination oxaliplatin, capecitabine, and trastuzumab with chemoradiotherapy in the adjuvant setting in participants with curatively resected HER2+ gastric or gastroesophageal junction cancer. Participants will receive trastuzumab 8 milligrams per kilogram (mg/kg) intravenously (IV) on Day 1 of Cycle 1 and 6 mg/kg IV on Day 1 of every following 3-week cycle, with oxaliplatin 100 milligrams per square meter (mg/m^2) IV on Day 1 of Cycles 1-3, and capecitabine 850 mg/m^2 orally twice daily on Days 1-14 of Cycles 1-3 and on 5 days per week during chemoradiotherapy. Radiotherapy will be given at a total dose of 45 gray (Gy) divided into 25 doses on 5 treatment days each week for 5 weeks starting Day 22 of Cycle 3. Anticipated time on study treatment is 1 year plus a 1-year follow-up period.

Official Title
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Safety and Tolerability of Oxaliplatin-Capecitabine-Trastuzumab Combination and Chemoradiotherapy in Operated Patients With HER-2 Positive Gastric or Gastroesophageal Junction Adenocarcinoma: Phase II Study, TOXAG [ML25574]

Conditions
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Gastric Cancer, Gastroesophageal Junction Cancer

Intervention / Treatment
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* Drug: Oxaliplatin
* Radiation: Radiation
* Drug: Capecitabine
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Curatively resected HER2+ gastric or gastroesophageal junction adenocarcinoma; HER2+ status as defined by immunohistochemistry-2 positive or 3 positive with corroborative Fluorescence In Situ Hybridization+ result Participants with stages between Stage IB (T1N1M0) and Stage IIIC ECOG performance status score equal to or less than (<=) 2 during screening Left ventricular ejection fraction equal to or higher than (>=) 55% with acceptable levels of liver and renal functions No known contraindication to capecitabine, oxaliplatin, and trastuzumab No contraindication for radiotherapy or has not received any previous radiotherapy to the gastric region for any reason Exclusion Criteria: Participants with a malign condition in the last 5 years except squamous cell carcinoma of the skin Previous neoadjuvant chemotherapy and/or radiotherapy Any disruption in the physical integrity of the upper gastrointestinal tract (except surgical intervention for gastric or gastroesophageal junction carcinoma) Known (previously diagnosed and ongoing) malabsorption syndrome Active gastrointestinal bleeding Participants with Stage IV gastric or gastroesophageal junction adenocarcinoma Clinically significant cardiac or cardiovascular disease Uncontrolled hypertension Participants who have received any investigational anti-cancer treatment or are being treated in a concomitant investigational drug study Abnormal laboratory values at screening for serum total bilirubin, alanine aminotransferase or aspartate amino transferase, alkaline phosphatase, absolute neutrophil count, platelet count, and/or hemoglobin Known or suspected hypersensitivity against trastuzumab or proteins of rodents Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Therapy<br>Participants will receive combination therapy comprising of trastuzumab, oxaliplatin, capecitabine, and radiation. | Drug: Oxaliplatin<br>* Participants will receive oxaliplatin 100 mg/m^2 IV on Day 1 of Cycles 1-3.<br>Radiation: Radiation<br>* Participants will receive radiotherapy at total dose of 45 Gy divided into 25 doses, 5 treatments per week for 5 weeks starting on Day 1 of Cycle 4.<br>Drug: Capecitabine<br>* Participants will receive capecitabine 850 mg/m^2 orally twice daily on Days 1-14 of Cycles 1-3 and on 5 days per week during chemoradiotherapy.<br>Drug: Trastuzumab<br>* Participants will receive trastuzumab 8 mg/kg IV on Day 1 Cycle 1, 6 mg/kg IV on Day 1 of each following 3-week cycle for 12 months (a total of 17 doses).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Baseline up to Month 13 | 
| Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Score |  | From Baseline to Month 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Disease-Free Survival, Using Response Evaluation Criteria for Solid Tumors (RECIST) |  | Cycle 1 Day 1 up to tumor relapse or death due to any reason, whichever occurs first (up to 24 months) | 
| Overall Survival |  | Cycle 1 Day 1 up to death due to any reason (up to 24 months) |