A Randomised Phase Ii Study Of Pre-Operative Or Peri-Operative Docetaxel, Oxaliplatin, Capecitabine (Dox) Regimen In Patients With Locally Advanced Resectable Gastric Cancer
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Gastric Cancer
- Sponsor
- Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
- Enrollment
- 106
- Locations
- 20
- Primary Endpoint
- the difference in percentage of patients receiving all the planned chemotherapeutic cycles between the two arms.
- Status
- Completed
- Last Updated
- last year
Overview
Brief 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
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consents
- •Male or female 18-75 years of age
- •Diagnosis of histologically confirmed, potentially resectable adenocarcinoma of the stomach
- •cT3 subserosal - cT4a - cT4b (7th edition UICC TNM) or bulky lymph node metastases independently of T
- •ECOG performance status of 0-1 at study entry
- •Laboratory requirements (≤ 7 days prior chemotherapy start):
- •Hematology:
- •I) Neutrophils \> 1.5 x 109 /L II) Platelets \> 100 x 109 /L III) Hemoglobin \> 10g/dL
- •Hepatic function I) Total bilirubin \< 1.25 UNL II) AST (SGOT) and ALT (SGPT) \< 2.5xUNL III) Alkaline phosphatase \< 2.5xUNL
- •Renal function I) Creatinine \<1.5 UNL In the event of border-line values, the calculated creatinine clearance should be \> 60 mL/min;
Exclusion Criteria
- •Early gastric cancer (if N0)
- •T2 (according to 7th edition of UICC TNM) if N0
- •Linitis plastica
- •Positive peritoneal cytology
- •Distant metastases
- •Neoplasm involving the gastro-esophageal junction
- •Pertoneal involvement
- •Concurrent chronic systemic immune therapy
- •Any investigational agent(s) administered 4 weeks prior to entry
- •Clinically relevant coronary artery disease, a history of myocardial infarction or of hypertension not controlled by therapy within the last 12 months
Outcomes
Primary Outcomes
the difference in percentage of patients receiving all the planned chemotherapeutic cycles between the two arms.
Time Frame: 7 years
Secondary Outcomes
- The percentage of tumors downstaged at the diagnosis(7 years)
- Treatment tolerability and safety and tumor response in patients with pathological stage pT1-3 vs pT0(7 years)
- Efficacy comparation between curative vs palliative surgery(7 years)
- Diagnostic capability of PET(7 years)
- Diagnostic capability of CT scan, CT/PET and laparoscopy(7 years)
- Biological profile of treatment toxicity(7 years)
- Biologcal profile of treatment response(7 years)
- Number of patients with adverse events of grade 3-4 as a measure of safety and tolerability(7 years)
- Time to progression(7 years)
- Overall survival(7 years)
- Biological profile of treatment prognosis(7 years)