Pre-Operative Or Peri-Operative Dox Regimen In Patients With Locally Advanced Resectable Gastric Cancer
Condition: Gastric Cancer; Locally Advanced Malignant Neoplasm
MeSH terms: Stomach Neoplasms; Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Study design:

      Multicenter, randomized, open label phase II study Arm A: DOX 4 cycles - Surgery - Follow-up
      Arm B: DOX 2 cycles - Surgery - DOX 2 cycles - Follow-up

      Population:

      Male or female, 18-75 years of age, with a diagnosis of histologically confirmed, potentially
      resectable adenocarcinoma of the stomach.

      Sample Size: Planned sample size is 90 patients, 45 patients for each arm (p0=50%, p1=80%,
      alpha=0.05 (two sides), beta=0.2)

      Treatment Plan:

      Treatment will be administered for 4 and 2 cycles before surgery in arm A and B,
      respectively, and in arm B for a further 2 cycles after surgery unless progression or
      unacceptable toxicity occurs, or a patient refuses treatment. In such cases patients will go
      off treatment. 3-6 weeks after the end of the fourth (arm A) or second (arm B) preoperative
      cycle, patients will undergo surgery.

      After surgery 3-6 weeks from surgery patients in arm B will receive 2 more cycles.

      DOX: Docetaxel 35 mg/m2 day 1 and 8 Oxaliplatin 80 mg/m2 day 1 Capecitabine 750 mg/m2 x 2
      daily for 2 weeks

      Cycles repeated every 3 weeks

      Evaluation criteria: Tumor assessment will be performed according to the RECIST criteria
      (version 1.1).

      Duration of Study:

      Overall study duration: 07/2010- 03/2017 Planned study duration per patient: 5 years
    

Detailed description: 
      Title: A randomised phase II study of pre-operative or peri-operative docetaxel, oxaliplatin,
      capecitabine (DOX) regimen in patients with locally advanced resectable gastric cancer.

      Clinical Phase: II

      Study Objectives:

      Primary:

      The percentage of patients receiving all the planned chemotherapeutic cycles.

      Secondary:

        -  Downstaging according to Recist criteria

        -  pT1-3 vs pT0.

        -  Safety: number of patients with grade 3-4 toxicity

        -  The role of PET Scan as predictor of response

        -  Curative vs palliative surgery

        -  TTP

        -  OS

        -  Diagnostic correlation between the various staging methods

        -  Possible correlations between CT scan, CT/PET, laparoscopy;

        -  Molecular markers related to toxicity: DPYD, MTHFR, TS, XPD, ERCC1, XRCC1;

        -  Molecular markers related to prognosis: TYMS, GSTP1, COX-2, RUNX3, methylation profile
           (Cox2, hMLH1, MGMT);

        -  Molecular markers related to therapy response: TYMS, DPYD, MTHFR, OPRT, ERCC1,
           XRCC1/2/3, GSTP1, GSTM1, GSTT1, ABCB1, methylation profile (Cox2, hMLH1, MGMT), whole
           genome arrayCGH.

      Study design:

      Multicenter, randomized, open label phase II study Arm A: DOX 4 cycles - Surgery - Follow-up
      Arm B: DOX 2 cycles - Surgery - DOX 2 cycles - Follow-up

      Population:

      Male or female, 18-75 years of age, with a diagnosis of histologically confirmed, potentially
      resectable adenocarcinoma of the stomach.

      Sample Size: Planned sample size is 90 patients, 45 patients for each arm (p0=50%, p1=80%,
      alpha=0.05 (two sides), beta=0.2)

      Treatment Plan:

      Treatment will be administered for 4 and 2 cycles before surgery in arm A and B,
      respectively, and in arm B for a further 2 cycles after surgery unless progression or
      unacceptable toxicity occurs, or a patient refuses treatment. In such cases patients will go
      off treatment. 3-6 weeks after the end of the fourth (arm A) or second (arm B) preoperative
      cycle, patients will undergo surgery.

      After surgery 3-6 weeks from surgery patients in arm B will receive 2 more cycles.

      DOX: Docetaxel 35 mg/m2 day 1 and 8 Oxaliplatin 80 mg/m2 day 1 Capecitabine 750 mg/m2 x 2
      daily for 2 weeks

      Cycles repeated every 3 weeks

      Evaluation criteria: Tumor assessment will be performed according to the RECIST criteria
      (version 1.1).

      Duration of Study:

      Overall study duration: 07/2010- 03/2017 Planned study duration per patient: 5 years
    

Intervention name(s): DOX 4 cycles - Surgery; DOX 2 cycles - Surgery - DOX 2 cycles
Intervention type(s): Other; Other
Intervention description(s): DOX 4 cycles - Surgery; DOX 2 cycles - Surgery - DOX 2 cycles
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Locally; Advanced; Resectable; Gastric Cancer