Clinical trial NCT01876927: Pre-Operative Or Peri-Operative Dox Regimen In Patients With Locally Advanced Resectable Gastric Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Cancer
Locally Advanced Malignant Neoplasm
Keywords: Locally
Advanced
Resectable
Gastric Cancer
Lead sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Sponsor class: OTHER
First posted: 2013-06-13
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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)

Primary outcomes:
measure: the difference in percentage of patients receiving all the planned chemotherapeutic cycles between the two arms.
timeFrame: 7 years
Secondary outcomes:
measure: The percentage of tumors downstaged at the diagnosis
timeFrame: 7 years
measure: Treatment tolerability and safety and tumor response in patients with pathological stage pT1-3 vs pT0
timeFrame: 7 years
measure: Number of patients with adverse events of grade 3-4 as a measure of safety and tolerability
timeFrame: 7 years
measure: Diagnostic capability of PET
timeFrame: 7 years
measure: Efficacy comparation between curative vs palliative surgery
timeFrame: 7 years
measure: Time to progression
timeFrame: 7 years
measure: Overall survival
timeFrame: 7 years
measure: Diagnostic capability of CT scan, CT/PET and laparoscopy
timeFrame: 7 years
measure: Biological profile of treatment toxicity
timeFrame: 7 years
measure: Biological profile of treatment prognosis
timeFrame: 7 years
measure: Biologcal profile of treatment response
timeFrame: 7 years
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - GM Lancisi
state: AN
city: Bibbiena
country: Italy
facility: USL 8 Arezzo - Presidio Ospedaliero Zona Casentino - Ospedale di Bibbiena
state: AR
city: Montevarchi
country: Italy
facility: USL 8 Arezzo - Ospedale "Santa Maria alla Gruccia"
state: AR
city: Brescia
country: Italy
facility: UO Oncologia , Spedali Civili di Brescia
state: BS
city: Cesena
country: Italy
facility: Ospedale Bufalini
state: FC
city: Meldola (FC)
country: Italy
facility: UO oncologia medica IRCCS IRST
state: FC
city: Empoli
country: Italy
facility: UOC Oncologia , Azienda USL 11
state: FI
city: Firenze
country: Italy
facility: Ospedale Careggi
state: FI
city: Milano
country: Italy
facility: UO ONCOLOGIA , Istituto Europeo di Oncologia
state: MI
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: MI
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
state: PI
city: Pavia
country: Italy
facility: UO Oncologia, Fondazione Policlinico San Matteo
state: PV
city: Rimini
country: Italy
facility: UO Oncologia Medica, PO Rimini, AUSL della Romagna
state: RI
city: Salerno
country: Italy
facility: UO Oncologia , Casa di Cura Tortorella
state: SA
city: Siena
country: Italy
facility: Policlinico Le Scotte
state: SI
city: Treviglio
country: Italy
facility: UO Oncologia, Azienda Ospedaliero Treviglio
state: TV
city: Varese
country: Italy
facility: UO Oncologia Medica, azienda Ospedaliera di Varese
state: VA
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia
city: Roma
country: Italy
facility: Ospedale San Filippo Neri
city: Verona
country: Italy
facility: Ospedale Borgo Trento
Study officials:
affiliation: IRST IRCCS, Meldola
name: Manlio Monti, MD
role: PRINCIPAL_INVESTIGATOR
References: