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 (TOXAG)

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]

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Gastroesophageal Junction Cancer
• Intervention / Treatment: Drug: Oxaliplatin; Radiation: Radiation; Drug: Capecitabine; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Turkey
  • Adana, Turkey, 01250
    • Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
  • Ankara, Turkey, 06200
    • Ankara Oncology Hospital; Oncology
  • Ankara, Turkey, 06100
    • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
  • Ankara, Turkey, 06490
    • Baskent University Medical Faculty; Internal Medicine
  • Gaziantep, Turkey, 27310
    • Gaziantep University Medical Faculty, Medical Oncology Department
  • Istanbul, Turkey, 34890
    • Marmara Uni Faculty of Medicine; Medical Oncology
  • Izmir, Turkey, 35100
    • Ege Uni Medical Faculty; Oncology Dept
  • Konya, Turkey, 42080
    • Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases
  • Çankaya/Ankara, Turkey, 06800
    • Bilkent Sehir Hospita; ONKOLOJI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination Therapy; Participants will receive combination therapy comprising of trastuzumab, oxaliplatin, capecitabine, and radiation.

Drug: Oxaliplatin; Participants will receive oxaliplatin 100 mg/m^2 IV on Day 1 of Cycles 1-3.; Radiation: Radiation; 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.; Drug: Capecitabine; 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.; Drug: Trastuzumab; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Abali H, Yalcin S, Onal HC, Dane F, Oksuzoglu B, Ozdemir N, Mertsoylu H, Artac M, Camci C, Karabulut B, Basal FB, Budakoglu B, Sendur MAN, Goktas B, Ozdener F, Baygul A. A Phase II Study of the Combination of Oxaliplatin, Capecitabine, and Trastuzumab and Chemoradiotherapy in the Adjuvant Setting in Operated Patients With HER2-positive Gastric or Gastroesophageal Junction Cancer (TOXAG Study): A Turkish Oncology Group Study. Am J Clin Oncol. 2021 Jul 1;44(7):301-307. doi: 10.1097/COC.0000000000000825.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2013
• Primary Completion (Actual): August 21, 2015
• Study Completion (Actual): June 15, 2017

Study Registration Dates

• First Submitted: December 10, 2012
• First Submitted That Met QC Criteria: December 12, 2012
• First Posted (Estimate): December 13, 2012

Study Record Updates

• Last Update Posted (Actual): October 9, 2019
• Last Update Submitted That Met QC Criteria: October 7, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Capecitabine; Oxaliplatin
• Other Study ID Numbers: ML25574