Locally Advanced Unresectable Gastric Cancer, Metastatic Gastric Cancer
Conditions
Brief summary
This is a randomized, parallel group, non-blinded phase III trial. Patients with advanced (locoregional or metastatic) gastric cancer not previously treated with chemotherapy for this stage will be randomized in a 1:1 ratio to receive low-TOX (arm A) or EOX (arm B). Randomization will be stratified by performance status (ECOG 0, 1 and 2).
Detailed description
Although the incidence of the adenocarcinoma of the stomach is slowly decreasing, gastric cancer represents the second worldwide cause of cancer death after lung cancer. In patients with advanced disease, chemotherapy improves survival and quality of life. Combinations of two or three drugs including a platin derivative (cisplatin or oxaliplatin), a fluoropyrimidine (5FU or capecitabine) and an anthracycline (usually epirubicin) have demonstrated superiority compared to single or double agent therapy and are the current standard. As of today there are no published studies comparing anthracycline-based to taxane-based three-drug regimens. The objective of the present study is to compare EOX as evaluated in REAL-2 to the low-TOX regimen consisting of docetaxel, oxaliplatin and capecitabine. Low-TOX is expected to be better tolerated than the original DCF regimen. The study will be performed in the HER2 negative patients.
Interventions
DRUGDocetaxel
Powder for solution for infusion
DRUGEpirubicin
Solution for infusion
DRUGOxaliplatin
Powder for solution for infusion
DRUGCapecitabine
Film coated tablets
Sponsors
Regione Lombardia
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent prior to beginning protocol specific procedures * Male or female \> 18 years of age * Histologically proven diagnosis of adenocarcinoma of the stomach * HER2 negative tumor or HER2+ tumors not qualifying for herceptin therapy * Locally advanced (non resectable) or metastatic gastric cancer * Presence of measurable disease with at least one measurable lesion by means of CT scan or MRI in not previously irradiated area(s) (according to RECIST criteria (version 1.1) * Life expectancy of \>/= 3 months * ECOG performance status of 0-2 at study entry * Neutrophils \>/= 2.0 x 1000000000/L, platelets \>/= 100 x 1000000000/L, and hemoglobin \>/= 10 g/dL * Bilirubin level either normal or \</= 1.5 x ULN * AST and ALT \</= 2.5 X UNL (\</= 5 x ULN if liver metastasis are present * Alkaline phosphatase (ALP) \</= 2.5 X ULN; patients with alkaline phosphatase \> 2.5x ULN and AST and ALT \</= 1.5 x ULN are equally eligible * Serum creatinine \< 1.5 x ULN. In presence border-line values, the calculated creatinine clearance should be \>/= 60 mL/min * Negative pregnancy test (if female in reproductive years) * Effective contraception prior to study entry and for the duration of the study participation, for both male and female patients of child producing potential * Able and willing to comply with scheduled visits, therapy plans and laboratory tests required in this protocol
Exclusion criteria
* Previous chemotherapy, except adjuvant treatment administered at least 1 year before study entry * Concurrent chronic systemic immune therapy * Any investigational agent(s) 4 weeks prior to entry * Clinically relevant coronary artery disease or a history of a myocardial infarction or a history of hypertension not controlled by therapy within the last 12 months * Known hypersensitivity to study drugs. Known grade 3 or 4 allergic reaction to any of the components of the treatment * Known drug abuse/ alcohol abuse * Acute or subacute intestinal occlusion and any other significant chronic gastrointestinal disease that might interfere with absorption of oral treatment * History of clinically relevant psychiatric disability precluding informed consent * Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule * Pregnant or breastfeeding women * Active uncontrolled infection(s) * Positive for HIV serology and/or viral hepatitis B or C * Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Measured as the time from randomization to the date of local or regional progression, distant metastasis, second primary malignancy or death, assessed up to 18 months of follow up | To determine the progression free survival (PFS) of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Measured as the time from randomization to the date of death from any cause, assessed up to 18 months of follow up | To assess overall survival (OS) of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B) |
| Objective Response Rate (CR + PR) according to RECIST 1.1 guideline | Measured as the time from randomization, assessed up to 18 months of follow up | To assess objective response rate (CR+PR)of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B) |
| Disease control rate: CR + PR + SD lasting > 12 weeks | Measured as the time from randomization, assessed up to 18 months of follow up | To assess disease control rate of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B) |
| Tolerability of the treatments evaluated in term of occurrence of: side effects graded according to the NCI-CTCAE scale (version 4.0); serious adverse reactions, expected and unexpected | Measured as the time from randomization, assessed up to 18 months of follow up | To assess tolerability of the treatments of patients with locally advanced unresectable or metastatic gastric cancer treated with Docetaxel plus Oxaliplatin plus Capecitabine (Arm A) or with Epirubicin plus Oxaliplatin plus Capecitabine (Arm B) |
Countries
Italy
Outcome results
None listed