TOXAG: 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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01748773

Collaborator

(none)

Enrollment

Locations

Arm

52.5

Actual Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer Gastroesophageal Junction Cancer	Drug: Oxaliplatin Radiation: Radiation Drug: Capecitabine Drug: Trastuzumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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]

Actual Study Start Date :

Jan 29, 2013

Actual Primary Completion Date :

Aug 21, 2015

Actual Study Completion Date :

Jun 15, 2017

Arms and Interventions

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).

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).

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana	Turkey	01250
2	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Ankara	Turkey	06100
3	Ankara Oncology Hospital; Oncology	Ankara	Turkey	06200
4	Baskent University Medical Faculty; Internal Medicine	Ankara	Turkey	06490
5	Gaziantep University Medical Faculty, Medical Oncology Department	Gaziantep	Turkey	27310
6	Marmara Uni Faculty of Medicine; Medical Oncology	Istanbul	Turkey	34890
7	Ege Uni Medical Faculty; Oncology Dept	Izmir	Turkey	35100
8	Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases	Konya	Turkey	42080
9	Bilkent Sehir Hospita; ONKOLOJI	Çankaya/Ankara	Turkey	06800

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01748773

Other Study ID Numbers:

ML25574

First Posted:

Dec 13, 2012

Last Update Posted:

Oct 9, 2019

Last Verified:

Oct 1, 2019

Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 9, 2019