Optimal Duration of Oxaliplatin in Adjuvant XELOX for Gastric Cancer Patients (EXODOX)

Sponsor

Hallym University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04787354

Collaborator

(none)

976

Enrollment

Location

Arms

Anticipated Duration (Months)

13.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to compare the efficacy and safety of reduced adjuvant XELOX treatment (4 cycles of XELOX followed by 4 cycles of capecitabine alone) to standard adjuvant XELOX treatment (8 cycles of XELOX).

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: Oxaliplatin Drug: Capecitabine	Phase 3

Detailed Description

XELOX (oxaliplatin + capecitabine) combination chemotherapy is considered a standard adjuvant treatment for curatively resected gastric cancer patients after it proved its effecacy in the CLASSIC trial. Adjuvant XELOX chemotherapy is a long-term treatment with a total treatment period of 6 months and it is known that about 33% of patients cannot complete treatment schedule due to side effects. In particular, peripheral neuropathy, which is caused by the cumulative administration of oxaliplatin, is a major cause of lowering the patient's quality of life and treatment compliance, and it is known that the incidence rate increases when standard XELOX treatment is continued for more than 6 cycles. In colorectal cancer, clinical studies have been actively conducted to shorten the duration of standard adjuvant chemotherapy to reduce the peripheral sensory neuropathy caused by oxaliplatin, but there are no relevant studies in gastric cancer.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

976 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase 3 Clinical Trial Investigating Optimal Duration of Oxaliplatin Administration in Postoperative XELOX (Oxaliplatin + Capecitabine) Adjuvant Chemotherapy for the Patients With Stage II/III Gastric Cancer

Actual Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control arm Standard adjuvant XELOX 8 cycles Oxaliplatin: 130 mg/m2/day(day 1) Capecitabine: 2,000 mg/m2/day(day 1-14), q 3weeks, total 8 cycles	Drug: Oxaliplatin Oxaliplatin: 130 mg/m2/day Drug: Capecitabine Capecitabine: 2,000 mg/m2/day
Experimental: Study arm Adjuvant XELOX 4 cycles followed by capecitabine monotherapy 4 cycles Oxaliplatin: 130 mg/m2/day(day 1) Capecitabine: 2,000 mg/m2/day(day 1-14), q 3weeks, 4 cycles followed by Capecitabine: 2,000 mg/m2/day(day 1-14), q 3weeks, 4 cycles	Drug: Oxaliplatin Oxaliplatin: 130 mg/m2/day Drug: Capecitabine Capecitabine: 2,000 mg/m2/day

Arm

Intervention/Treatment

Active Comparator: Control arm

Standard adjuvant XELOX 8 cycles Oxaliplatin: 130 mg/m2/day(day 1) Capecitabine: 2,000 mg/m2/day(day 1-14), q 3weeks, total 8 cycles

Drug: Oxaliplatin

Oxaliplatin: 130 mg/m2/day

Drug: Capecitabine

Capecitabine: 2,000 mg/m2/day

Experimental: Study arm

Adjuvant XELOX 4 cycles followed by capecitabine monotherapy 4 cycles Oxaliplatin: 130 mg/m2/day(day 1) Capecitabine: 2,000 mg/m2/day(day 1-14), q 3weeks, 4 cycles followed by Capecitabine: 2,000 mg/m2/day(day 1-14), q 3weeks, 4 cycles

Drug: Oxaliplatin

Oxaliplatin: 130 mg/m2/day

Drug: Capecitabine

Capecitabine: 2,000 mg/m2/day

Outcome Measures

Primary Outcome Measures

disease-free survival [3-year]
The disease-free survival (DFS) will be measured from the start of study treatment until documented tumor progression (by RECIST) or death due to any cause

Secondary Outcome Measures

overall survival [5-year]
The overall survival (OS) will be estimated from the start of study treatment until participant's death and measured using the Kaplan-Meier method
Toxicity profiles [3-year]
Adverse events will be graded using the NCI common terminology criteria for adverse events (NCTCAE) v 5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma patients who underwent curative surgery (D1 beta or D2 resection)
Pathologically confirmed stage II, III patients (AJCC 8th edition)
Age 19 years and older
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 2
Adequate marrow function (ANC > 1,500/uL, Platelet >100,000/uL, Hb > 8.0 g/dL, patients with chronic anemia who require intermittent blood transfusions can also participate in the study)
Adequate renal function, with serum creatinine < 1.5 x upper limit of normal (ULN).
Adequate hepatic function with serum total bilirubin ≤ 1.5 x ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
Written, informed consent to the study

Exclusion Criteria:

Female patients who are pregnant or breast-feeding
Positive pregnancy test at baseline (postmenopausal women should be amenorrhea for at least 12 months to be considered non-fertile)
Sexually active men and women who are not willing to implement contraception during study and until 3 months after discontinuation of study drug
Evidence of metastasis (including cytologically confirmed malignant ascites)
Prior systemic chemotherapy or radiation therapy for stomach cancer
Patients who have not recovered from serious complications of gastrectomy
History of other malignancies within the last 3 years (excluding adequately treated basal cell carcinoma of the skin, in situ cancer of the cervix, non-metastatic thyroid cancer)
A history of clinically significant uncontrolled seizures, central nervous system disorders, or mental disorders, which make it impossible to understand the informed consent or interfere with compliance with oral drug intake
Clinically significant (i.e., active) heart disease: e.g. unstable angina requiring medication, symptomatic coronary artery disease, congestive heart failure with NYHA grade II or higher, severe cardiac arrhythmias or acute coronary syndrome in the past 6 months (including myocardial infarction)
Lack of integrity or malabsorption syndrome in the upper gastrointestinal tract, which is likely to affect the absorption of study drug
Serious uncontrolled infection or other serious uncontrolled disease
History of allograft requiring immunosuppression therapy
Received any investigational drug or procedure within 4 weeks prior to randomization
Active viral infection (for hepatitis B carrier, patients can be registered if HBV-DNA titer is less than 20,000 IU/mL, and are allowed to use prophylactic antiviral agents by investigator's choice)
Active HIV infection
Patients with peripheral sensory neuropathy with functional impairment