Clinical trial NCT01830270: Preoperative Dose-dense Chemotherapy With Weekly Cisplatin, Epirubicin and Paclitaxel to Treat Patients With Locally Gastric Cancer
Official title: Preoperative Chemotherapy With Weekly Cisplatin, Epirubicin and Paclitaxel (Intensified PET) in Patients With Locally Gastric Cancer : a Phase II Proof-of-concept Study.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Stomach Neoplasms
Oesophageal Junction Cancer
Lower Oesophagus Cancer
Keywords: medical oncology
chemotherapy optimization
dose density
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
First posted: 2013-04-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: If surgery remains the main treatment for gastric cancer without distant metastases; perioperative-chemotherapy increased the likelihood of progression free survival. Perioperative chemotherapy appears to have many advantages : to reduce the tumor volume, to improve the R0 resection rate, and to act on micro-metastases. Therefore, peri-operative chemotherapy combining cisplatin, epirubicin and 5-Fluorouracile is a validated strategy to treat gastric cancer. However, several pitfalls remained. Particularly, only 42% of patients could received post-chemotherapy, due to post-operative complications and toxicities. To overcome this limitation, the investigators will conduct a phase II clinical trial assessing the clinical interest of a dose-dense preoperative chemotherapy combining cisplatin (P), epirubicin (E) and paclitaxel (T). The increasing evidence of taxane's role in gastric cancer treatment, as well as the biological synergisms reported in paclitaxel/cisplatin and paclitaxel/epirubicin combinations, sustain the development of dose density based on PET combination in gastric carcinoma. The aim of the IPEC-GC study is to evaluate the effectiveness of this PET preoperative regimen

Detailed description: The IPEC-GC study is a proof-of-concept study evaluating the efficacy and feasibility of PET regimen in 61 patients with lower oesophagus, oesophagus junction or gastric carcinoma.

Preoperative chemotherapy include eight weekly preoperative cycles of cisplatin (30mg/m2), epirubicin (50 mg/m2) and paclitaxel (90 mg/m2)with a break of one week without chemotherapy between cycle 4 and 5. Surgery is performed within 4-6 weeks after the end of the last cycle of chemotherapy. Primary endpoint of this trial is the curative resection rate (=R0). R0 must be higher than the 79% achieved in previous published studies. Response rate, histologic response rate (Becker score), progression-free survival, overall survival, impact of complete response in survival and dose-density are secondary endpoints. For an ancillary study, tumors (biopsies and operative specimens) and sera will be collected to identify biomarkers correlated with treatment efficacy.

This study is carried out by the Besançon University Hospital and were approved by the independent Est-II ethics committee and by the French National Authority for Health: AFSSAPS.

Eligibility criteria: Inclusion criteria :

* Age \> 18 and \< 70 years (male and female)
* surgical resectability
* ECOG performance status ≤ 1
* ASA score \< 3 (appreciation by a surgeon)
* BMI \< 30 if an upper oesogastrectomy is required
* no previous cytotoxic chemotherapy
* ejection fraction \> 50% in echocardiography before start of therapy
* written informed consent

Non-inclusion criteria :

* distant metastases or infiltration of adjacent structures or organs and all primarily not resectable stages
* relapse
* hypersensitivity against Paclitaxel, Epirubicin or Cisplatin
* malignant secondary disease, dated back \< 5 years (exception: in situ carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
* peripheral polyneuropathy
* diabetes complicated by coronary artery disease or vasculopathy
* Severe respiratory insufficiency
* patient with weight loss \> 10%
* pregnancy or lactation
* inclusion in another trial
* patient with any medical or psychiatric condition or disease which would make the patient inappropriate for entry into this study.

Primary outcomes:
measure: curative resection rate
timeFrame: an expected average of 4 weeks after surgery
Secondary outcomes:
measure: response rate
timeFrame: between 2 and 4 weeks after the end of the last cycle of chemotherapy
measure: histologic response rate
timeFrame: an expected average of 4 weeks after surgery
measure: tolerance of the therapeutic association
timeFrame: 1 week after each chemotherapy cycle
measure: progression free survival
timeFrame: from date to initiation of chemotherapy until the date of first documented progression (within 5 years after surgery)
measure: global survival
timeFrame: from date to initiation of chemotherapy until the date of death for any cause (within 5 years after surgery)
Other outcomes:
Locations:
city: Besançon
country: France
facility: University hospital of Besançon
city: Dijon
country: France
facility: FNLCC center Georges François Leclerc
city: Montbeliard
country: France
facility: Hospital of Belfort-Montbeliard
Study officials:
References:
citation: Jary M, Ghiringhelli F, Jacquin M, Fein F, Nguyen T, Cleau D, Nerich V, El Gani M, Mathieu P, Valmary-Degano S, Arnould L, Lassabe C, Lamfichekh N, Fratte S, Paget-Bailly S, Bonnetain F, Borg C, Kim S. Phase II multicentre study of efficacy and feasibility of dose-intensified preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) in resectable gastroesophageal cancer. Cancer Chemother Pharmacol. 2014 Jul;74(1):141-50. doi: 10.1007/s00280-014-2482-0. Epub 2014 May 14.