Pre-Operative Or Peri-Operative Dox Regimen In Patients With Locally Advanced Resectable Gastric Cancer

Gastric Cancer Clinical Trial

— GastroDOC  

Official 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 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
• 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)

Related Conditions & MeSH terms

• Gastric Cancer
• Locally Advanced Malignant Neoplasm
• Neoplasms
• Stomach Neoplasms

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