Clinical trial NCT01748773: 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
Official title: 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]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Cancer
Gastroesophageal Junction Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-12-13
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Month 13
measure: Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Score
timeFrame: From Baseline to Month 13
Secondary outcomes:
measure: Percentage of Participants with Disease-Free Survival, Using Response Evaluation Criteria for Solid Tumors (RECIST)
timeFrame: Cycle 1 Day 1 up to tumor relapse or death due to any reason, whichever occurs first (up to 24 months)
measure: Overall Survival
timeFrame: Cycle 1 Day 1 up to death due to any reason (up to 24 months)
Other outcomes:
Locations:
city: Adana
country: Turkey
facility: Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
city: Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital; Oncology Dept
city: Ankara
country: Turkey
facility: Ankara Oncology Hospital; Oncology
city: Ankara
country: Turkey
facility: Baskent University Medical Faculty; Internal Medicine
city: Gaziantep
country: Turkey
facility: Gaziantep University Medical Faculty, Medical Oncology Department
city: Istanbul
country: Turkey
facility: Marmara Uni Faculty of Medicine; Medical Oncology
city: Izmir
country: Turkey
facility: Ege Uni Medical Faculty; Oncology Dept
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases
city: Çankaya/Ankara
country: Turkey
facility: Bilkent Sehir Hospita; ONKOLOJI
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.