Preoperative Dose-dense Chemotherapy With Weekly Cisplatin, Epirubicin and Paclitaxel to Treat Patients With Locally Gastric Cancer

Stomach Neoplasms Clinical Trial

— IPEC-GC  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01830270
• Other study ID #: IPEC-GC
• Status: Terminated
• Phase: Phase 2
• Start date: May 2011
• Est. completion date: July 2016

Study information

• Verified date: January 2016
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: July 2016
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Esophageal Neoplasms
• Lower Oesophagus Cancer
• Oesophageal Junction Cancer
• Stomach Neoplasms

Intervention

Drug:
• Epirubicin
8 weekly cycles of chemotherapy with epirubicin (50 mg/m2)associated with cisplatin and paclitaxel with a break of one week without chemotherapy between cycle 4 and 5.
• Cisplatin
8 weekly cycles of chemotherapy with cisplatin (30 mg/m2) associated with epirubicin and paclitaxel with a break of one week without chemotherapy between cycle 4 and 5.
• Paclitaxel
8 weekly cycles of chemotherapy with paclitaxel (90 mg/m2) associated with epirubicin and paclitaxel with a break of one week without chemotherapy between cycle 4 and 5.

Procedure:
• gastric surgery
surgery will be scheduled within 4-6 weeks after the end of the last cycle of chemotherapy.

Locations

Country	Name	City	State
France	University hospital of Besançon	Besançon
France	FNLCC center Georges François Leclerc	Dijon
France	Hospital of Belfort-Montbeliard	Montbeliard

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

References & Publications (1)

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, Fratté S, Paget-Bailly S, Bonnetain F, Borg C, Kim S. Phase II multicentre study of efficacy and feasibilit — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	curative resection rate		an expected average of 4 weeks after surgery
Secondary	response rate	Response rate will be evaluated using RECIST v1.1 criteria (Response Evaluation Criteria in Solid Tumors ; Eisenhauer et al, 2009) by a CT-scan done between 2 and 4 weeks after the end of the last cycle to verify the absence of local or distant progression before surgery	between 2 and 4 weeks after the end of the last cycle of chemotherapy
Secondary	histologic response rate	Histologic response rate will be determined by the pathologist laboratory on operative specimens using Becker's score (Becker et al, 2003) to measure effects of neoadjuvant chemotherapy on gastric cancer.	an expected average of 4 weeks after surgery
Secondary	tolerance of the therapeutic association	Toxicities will be evaluated using Common Terminology Criteria for Adverse Events version 4.	1 week after each chemotherapy cycle
Secondary	progression free survival		from date to initiation of chemotherapy until the date of first documented progression (within 5 years after surgery)
Secondary	global survival		from date to initiation of chemotherapy until the date of death for any cause (within 5 years after surgery)