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

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

Status and phase: Completed; Phase 2

Conditions: Locally Advanced Malignant Neoplasm; Gastric Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT01876927

IRST151.01

2010-020189-37 (EudraCT Number)

Details and patient eligibility

About

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

Full 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

Enrollment: 106 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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106 participants in 2 patient groups

Arm A

Experimental group

Description:

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.

Treatment:

Other: DOX 4 cycles - Surgery

Arm B

Experimental group

Description:

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.

Treatment:

Other: DOX 2 cycles - Surgery - DOX 2 cycles