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

NCT ID: NCT01876927

Last Updated: 2025-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2022-09-15

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

Conditions

Gastric Cancer; Locally Advanced Malignant Neoplasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

DOX 4 cycles - Surgery

Intervention Type: OTHER

DOX 4 cycles - Surgery

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.

Group Type: EXPERIMENTAL

DOX 2 cycles - Surgery - DOX 2 cycles

Intervention Type: OTHER

DOX 2 cycles - Surgery - DOX 2 cycles

Interventions

DOX 4 cycles - Surgery

DOX 4 cycles - Surgery

Intervention Type: OTHER

DOX 2 cycles - Surgery - DOX 2 cycles

DOX 2 cycles - Surgery - DOX 2 cycles

Intervention Type: OTHER

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manlio Monti, MD

Role: PRINCIPAL_INVESTIGATOR

IRST IRCCS, Meldola

Locations

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

USL 8 Arezzo - Ospedale "Santa Maria alla Gruccia"

Montevarchi, AR, Italy

UO Oncologia , Spedali Civili di Brescia

Brescia, BS, Italy

Ospedale Bufalini

Cesena, FC, Italy

UO oncologia medica IRCCS IRST

Meldola (FC), FC, Italy

UOC Oncologia , Azienda USL 11

Empoli, FI, Italy

Ospedale Careggi

Florence, FI, Italy

UO ONCOLOGIA , Istituto Europeo di Oncologia

Milan, MI, Italy

Istituto Clinico Humanitas

Rozzano, MI, Italy

Azienda Ospedaliera Universitaria Pisana

Pisa, PI, Italy

UO Oncologia, Fondazione Policlinico San Matteo

Pavia, PV, Italy

UO Oncologia Medica, PO Rimini, AUSL della Romagna

Rimini, RI, Italy

UO Oncologia , Casa di Cura Tortorella

Salerno, SA, Italy

Policlinico Le Scotte

Siena, SI, Italy

UO Oncologia, Azienda Ospedaliero Treviglio

Treviglio, TV, Italy

UO Oncologia Medica, azienda Ospedaliera di Varese

Varese, VA, Italy

Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia

Perugia, , Italy

Ospedale San Filippo Neri

Roma, , Italy

Ospedale Borgo Trento

Verona, , Italy

Countries

Italy

Other Identifiers

2010-020189-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IRST151.01

Identifier Type: -

Identifier Source: org_study_id