Pre-Operative Or Peri-Operative Dox Regimen In Patients With Locally Advanced Resectable Gastric Cancer
Conditions
Gastric Cancer - Locally Advanced Malignant Neoplasm
Conditions: official terms
Neoplasms - Stomach Neoplasms
Conditions: Keywords
Locally, Advanced, Resectable, Gastric Cancer
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: DOX 4 cycles - Surgery Type: Other
Name: DOX 2 cycles - Surgery - DOX 2 cycles Type: Other
Overall Status
Recruiting
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
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 75 Years
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Signed written informed consents

2. Male or female 18-75 years of age

3. Diagnosis of histologically confirmed, potentially resectable adenocarcinoma of the stomach

4. cT3 subserosal - cT4a - cT4b (7th edition UICC TNM) or bulky lymph node metastases independently of T

5. ECOG performance status of 0-1 at study entry

6. Laboratory requirements (≤ 7 days prior chemotherapy start):

1. Hematology:

I) Neutrophils > 1.5 x 109 /L II) Platelets > 100 x 109 /L III) Hemoglobin > 10g/dL

2. Hepatic function I) Total bilirubin < 1.25 UNL II) AST (SGOT) and ALT (SGPT) < 2.5xUNL III) Alkaline phosphatase < 2.5xUNL

3. Renal function I) Creatinine <1.5 UNL In the event of border-line values, the calculated creatinine clearance should be > 60 mL/min;

- Written informed consent signed and dated before randomization procedures, including expected cooperation of patients for treatment and follow-up, must be obtained and documented according to local regulatory requirements.

- Effective contraception for both male and female patients if the risk of conception exists

Exclusion Criteria:

1. Early gastric cancer (if N0)

2. T2 (according to 7th edition of UICC TNM) if N0

3. Linitis plastica

4. Positive peritoneal cytology

5. Distant metastases

6. Neoplasm involving the gastro-esophageal junction

7. Pertoneal involvement

8. Concurrent chronic systemic immune therapy

9. Any investigational agent(s) administered 4 weeks prior to entry

10. Clinically relevant coronary artery disease, a history of myocardial infarction or of hypertension not controlled by therapy within the last 12 months

11. Known grade 3 or 4 allergic reaction to any of the components of the treatment

12. Known drug abuse/alcohol abuse

13. Legal incapacity or limited legal capacity

14. Medical or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent

15. Women who are pregnant or breastfeeding

16. Acute or subacute intestinal occlusion

17. 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)
Locations
Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - GM Lancisi
Ancona, AN, Italy
Status: Recruiting
Contact: Stefano Cascinu, Prof.
USL 8 Arezzo - Presidio Ospedaliero Zona Casentino - Ospedale di Bibbiena
Bibbiena, AR, Italy
Status: Recruiting
Contact: Andrea Rinnovati, MD
USL 8 Arezzo - Ospedale "Santa Maria alla Gruccia"
Valdarno (Montevarchi), AR, Italy
Status: Recruiting
Contact: Gianni Mura, MD
UO Oncologia , Spedali Civili di Brescia
Brescia, BS, Italy
Status: Recruiting
Contact: Vittorio Ferrari, MD
Ospedale Bufalini
Cesena, FC, Italy
Status: Recruiting
Contact: Silvia Ruscelli, MD
UO oncologia medica IRCCS IRST
Meldola (FC), FC, Italy
Status: Recruiting
Contact: Manlio Monti, MD - +390543739266 - manlio.monti@irts.emr.it
UOC Oncologia , Azienda USL 11
Empoli, FI, Italy
Status: Recruiting
Contact: Carlo Milandri, MD
Ospedale Careggi
Firenze, FI, Italy
Status: Recruiting
Contact: Paolo Bechi, Prof.
UO ONCOLOGIA , Istituto Europeo di Oncologia
Milano, MI, Italy
Status: Recruiting
Contact: NICOLA FAZIO, MD
Istituto Clinico Humanitas
Rozzano, MI, Italy
Status: Recruiting
Contact: Armando Santoro, MD
Azienda Ospedaliera Universitaria Pisana
Pisa, PI, Italy
Status: Recruiting
Contact: Monica Lencioni, MD
UO Oncologia, Fondazione Policlinico San Matteo
Pavia, PV, Italy
Status: Recruiting
Contact: Silvia Brugnatelli, MD
UO Oncologia Medica, PO Rimini, AUSL della Romagna
Rimini, RI, Italy
Status: Recruiting
Contact: Emiliano Tamburini, MD
UO Oncologia , Casa di Cura Tortorella
Salerno, SA, Italy
Status: Recruiting
Contact: Carmine Calvanese, MD
Policlinico Le Scotte
Siena, SI, Italy
Status: Recruiting
Contact: Franco Roviello, Prof.
UO Oncologia, Azienda Ospedaliero Treviglio
Treviglio, TV, Italy
Status: Recruiting
Contact: Sandro Barni, MD
UO Oncologia Medica, azienda Ospedaliera di Varese
Varese, VA, Italy
Status: Recruiting
Contact: Ilaria Proserpio, MD
Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia
Perugia, Italy
Status: Recruiting
Contact: Verena De Angelis, MD
Ospedale San Filippo Neri
Roma, Italy
Status: Recruiting
Contact: Giacomo Moscati, MD
Ospedale Borgo Trento
Verona, Italy
Status: Recruiting
Contact: Giovanni De Manzoni, Prof.
Start Date
September 2010
Completion Date
March 2017
Sponsors
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Source
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page