Trial of Docetaxel, Oxaliplatin and Capecitabine (TEX) in Advanced or Metastatic Gastric Cancer

Phase II Trial of Docetaxel, Oxaliplatin and Capecitabine (TEX) in Advanced or Metastatic Gastric Cancer

Combination regimens of 3 active drugs have shown promising activity in treatment of metastatic gastric cancer. Docetaxel combined with cisplatin and 5-fluorouracil (FU) yielded superior overall survival and response rates when compared to standard cisplatin and 5-FU. However, a toxicity profile showed the need for development of less toxic modifications. In a prior phase I trial, the maximum tolerated dose was defined. In this phase II trial, a first evaluation of activity will be performed.

Inclusion Criteria:

• Written informed consent

• Histologically proven irresectable, metastatic or recurrent adenocarcinoma of the stomach or the gastroesophageal junction, i.e., Tx-4 M1 or T4 M0

• Irresectable (as judged by an experienced surgeon):

  1. T4 infiltrating of several organs
  2. T4 infiltrating one organ, but irresectable
  3. T4 infiltrating one organ, respectable, but inoperable patient

• The nodal status is neglected

• Measurable disease according to RECIST

• ECOG Performance Status ≤ 2

• Male or female patients aged ≥ 18 years

• Life expectancy ≥ 3 months

• Adequate bone marrow, hepatic and renal function:

  1. Haemoglobin > 9.0 g/dL (transfusions allowed to achieve or maintain levels)
  2. Absolute neutrophil count > 1.5 x 10^9/L
  3. Platelet count > 100 x 10^9/L
  4. ALAT, ASAT < 3.5 x ULN
  5. Alkaline phosphatase < 6 x ULN
  6. Total bilirubin < 1.0 x ULN
  7. Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault)

• Prior surgery must be more than 28 days ago

• Positive nodes as diagnosed on endorectal ultrasound and/or MRI (tumour is staged by preferably a high resolution MRI; if MRI is not available, locoregional staging must be performed by computed tomography plus endorectal ultrasound)

• Tumor staging must be done within 28 days from the start of the treatment

• Negative pregnancy test in women with childbearing of potential (within 7 days prior to the start of the chemotherapy)

  • Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential

Exclusion Criteria:

• Prior cytotoxic chemotherapy or radiotherapy (a neoadjuvant or adjuvant chemotherapy must be completed and without progression for at least 6 months)

• Previous (within the last 5 years) or concurrent malignancies, with the exception of adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin

• Peripheral neuropathy ≥ grade 2 (according to NCI CTCAE v 3.0)

• Patient must not have been treated with any investigational drug, agent nor procedure, (i.e., did not participate in another trial within 30 days) before entry in this trial

• Known allergy or any other adverse reaction to any of the study drugs or to any related compound

• Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine

• Clinically significant concomitant diseases, such as:

  1. Active infection necessitating systemic antibiotics
  2. Interstitial lung diseases
  3. Chronic diarrhea, inflammatory bowel disease
  4. Neurological or psychiatric disease, dementia, epilepsy or untreated brain metastases

• Cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction or resuscitation within the last 6 months

• Pregnant or lactating women are excluded

• Presence of adequate contraception in fertile patients (methods of adequate contraception are: intra-uterine device, hormonal contraception, vasectomy, tubal ligation or abstinence)

• Alcohol or drug abuse

• Ability to swallow tablets

• Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule