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

A Randomised Phase Ii Study Of Pre-Operative Or Peri-Operative Docetaxel, Oxaliplatin, Capecitabine (Dox) Regimen In Patients With Locally Advanced Resectable Gastric Cancer

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

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Locally Advanced Malignant Neoplasm
• Intervention / Treatment: Other: DOX 4 cycles - Surgery; Other: DOX 2 cycles - Surgery - DOX 2 cycles

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

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Perugia, Italy
    • Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia
  • Roma, Italy
    • Ospedale San Filippo Neri
  • Verona, Italy
    • Ospedale Borgo Trento
  • AN
    • Ancona, AN, Italy
      • Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - GM Lancisi
  • AR
    • Bibbiena, AR, Italy
      • USL 8 Arezzo - Presidio Ospedaliero Zona Casentino - Ospedale di Bibbiena
    • Montevarchi, AR, Italy
      • USL 8 Arezzo - Ospedale "Santa Maria alla Gruccia"
  • BS
    • Brescia, BS, Italy, 25123
      • UO Oncologia , Spedali Civili di Brescia
  • FC
    • Cesena, FC, Italy
      • Ospedale Bufalini
    • Meldola (FC), FC, Italy, 47014
      • UO Oncologia Medica IRCCS IRST
  • FI
    • Empoli, FI, Italy, 50053
      • UOC Oncologia , Azienda USL 11
    • Firenze, FI, Italy
      • Ospedale Careggi
  • MI
    • Milano, MI, Italy, 20141
      • UO ONCOLOGIA , Istituto Europeo di Oncologia
    • Rozzano, MI, Italy
      • Istituto Clinico Humanitas
  • PI
    • Pisa, PI, Italy
      • Azienda Ospedaliera Universitaria Pisana
  • PV
    • Pavia, PV, Italy, 27100
      • UO Oncologia, Fondazione Policlinico San Matteo
  • RI
    • Rimini, RI, Italy, 47923
      • UO Oncologia Medica, PO Rimini, AUSL della Romagna
  • SA
    • Salerno, SA, Italy, 84122
      • UO Oncologia , Casa di Cura Tortorella
  • SI
    • Siena, SI, Italy
      • Policlinico Le Scotte
  • TV
    • Treviglio, TV, Italy, 24047
      • UO Oncologia, Azienda Ospedaliero Treviglio
  • VA
    • Varese, VA, Italy, 21100
      • UO Oncologia Medica, azienda Ospedaliera di Varese

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; DOX 4 cycles - Surgery - Follow-up DOX: Docetaxel 35 mg/m2 day 1 and 8 by one hour infusion; Oxaliplatin 80 mg/m2 day 1 by two hours infusion; Capecitabine 750 mg/m2 x 2 daily for 2 weeks, per OS. Treatment should be administered for 4 cycles before surgery. Each cycle will be repeated every 3 weeks.	Other: DOX 4 cycles - Surgery; DOX 4 cycles - Surgery
Experimental: Arm B; DOX 2 cycles - Surgery - DOX 2 cycles - Follow-up DOX: Docetaxel 35 mg/m2 day 1 and 8 by one hour infusion; Oxaliplatin 80 mg/m2 day 1 by two hours infusion; Capecitabine 750 mg/m2 x 2 daily for 2 weeks, per OS. Treatment should be administered for 2 cycles before surgery and for further 2 cycles after surgery, unless progression of disease or unacceptable toxicity occurs, or patient refusal. In these cases patients will go off treatment. Each cycle will be repeated every 3 weeks.	Other: DOX 2 cycles - Surgery - DOX 2 cycles; DOX 2 cycles - Surgery - DOX 2 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the difference in percentage of patients receiving all the planned chemotherapeutic cycles between the two arms.	7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Number of patients with adverse events of grade 3-4 as a measure of safety and tolerability		7 years
Diagnostic capability of PET	Evaluation of the role of PET as a tool to detect tumor response	7 years
Efficacy comparation between curative vs palliative surgery		7 years
Time to progression		7 years
Overall survival		7 years
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
Biological profile of treatment toxicity	Biological detection of molecular markers related to treatment toxicity (DPYD, MTHFR, TS, XPD, ERCC1, XRCC1)	7 years
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
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

Collaborators and Investigators

• Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
• Investigators: Principal Investigator: Manlio Monti, MD, IRST IRCCS, Meldola

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): September 15, 2022

Study Registration Dates

• First Submitted: June 7, 2013
• First Submitted That Met QC Criteria: June 11, 2013
• First Posted (Estimated): June 13, 2013

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 8, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Gastric Cancer; Locally; Advanced; Resectable
• Additional Relevant MeSH Terms: Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms; Stomach Neoplasms
• Other Study ID Numbers: IRST151.01; 2010-020189-37 (EudraCT Number)