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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01876927
Other study ID # IRST151.01
Secondary ID 2010-020189-37
Status Completed
Phase Phase 2
First received June 7, 2013
Last updated July 19, 2017
Start date September 2010
Est. completion date March 2017

Study information

Verified date July 2017
Source Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


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


Recruitment information / eligibility

Status Completed
Enrollment 90
Est. completion date March 2017
Est. primary completion date March 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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)

Study Design


Related Conditions & MeSH terms


Intervention

Other:
DOX 4 cycles - Surgery
DOX 4 cycles - Surgery
DOX 2 cycles - Surgery - DOX 2 cycles
DOX 2 cycles - Surgery - DOX 2 cycles

Locations

Country Name City State
Italy Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - GM Lancisi Ancona AN
Italy USL 8 Arezzo - Presidio Ospedaliero Zona Casentino - Ospedale di Bibbiena Bibbiena AR
Italy UO Oncologia , Spedali Civili di Brescia Brescia BS
Italy Ospedale Bufalini Cesena FC
Italy UOC Oncologia , Azienda USL 11 Empoli FI
Italy Ospedale Careggi Firenze FI
Italy UO oncologia medica IRCCS IRST Meldola (FC) FC
Italy UO ONCOLOGIA , Istituto Europeo di Oncologia Milano MI
Italy UO Oncologia, Fondazione Policlinico San Matteo Pavia PV
Italy Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia Perugia
Italy Azienda Ospedaliera Universitaria Pisana Pisa PI
Italy UO Oncologia Medica, PO Rimini, AUSL della Romagna Rimini RI
Italy Ospedale San Filippo Neri Roma
Italy Istituto Clinico Humanitas Rozzano MI
Italy UO Oncologia , Casa di Cura Tortorella Salerno SA
Italy Policlinico Le Scotte Siena SI
Italy UO Oncologia, Azienda Ospedaliero Treviglio Treviglio TV
Italy USL 8 Arezzo - Ospedale "Santa Maria alla Gruccia" Valdarno (Montevarchi) AR
Italy UO Oncologia Medica, azienda Ospedaliera di Varese Varese VA
Italy Ospedale Borgo Trento Verona

Sponsors (1)

Lead Sponsor Collaborator
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary the difference in percentage of patients receiving all the planned chemotherapeutic cycles between the two arms. 7 years
Secondary The percentage of tumors downstaged at the diagnosis To determine the percentage of tumors downstaged at the diagnosis, compared with the pathological stage detected at the time of surgery (according to Recist criteria) 7 years
Secondary Treatment tolerability and safety and tumor response in patients with pathological stage pT1-3 vs pT0 Comparation of treatment tolerability and safety and tumor response between patients with pathological stage pT1-3 vs pT0 (detected at the time of surgery) 7 years
Secondary Number of patients with adverse events of grade 3-4 as a measure of safety and tolerability 7 years
Secondary Diagnostic capability of PET Evaluation of the role of PET as a tool to detect tumor response 7 years
Secondary Efficacy comparation between curative vs palliative surgery 7 years
Secondary Time to progression 7 years
Secondary Overall survival 7 years
Secondary Diagnostic capability of CT scan, CT/PET and laparoscopy Evaluation of possible correlations between the diagnostic techniques CT scan, CT/PET and laparoscopy 7 years
Secondary Biological profile of treatment toxicity Biological detection of molecular markers related to treatment toxicity (DPYD, MTHFR, TS, XPD, ERCC1, XRCC1) 7 years
Secondary Biological profile of treatment prognosis Biological detection of molecular markers related to treatment prognosis (TYMS, GSTP1, COX-2, RUNX3, methylation profile (Cox2, hMLH1, MGMT)) 7 years
Secondary Biologcal profile of treatment response Biological detection of 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) 7 years
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