Pepita

Prospective multicenter-interventional non-randomized phase II study

Primary

Examine the predictive value of PET-assessed tumour FDG uptake response after one course of preoperative chemotherapy on the outcome of adjuvant therapy, measured by 3-year DFS.

Secondary

• Examine the predictive value of PET-assessed tumour FDG uptake changes after one course of preoperative chemotherapy on OS
• Evaluate the best cut-off value for relative delta SUV in assessment of preoperative chemotherapy response by FDG-PET/CT imaging.
• Analyze the cost-effectiveness of preoperative chemo-sensitivity testing
• Translational research:
  • Assess the predictive value of CTCs on DFS
  • Assess the predictive value of SNPs on toxicity- and drug target-related genes on DFS
  • Create a frozen tumour bank for future studies

For entry in the screening phase of the study:

• Age 18 years or older
• Clinical/radiological evaluation compatible with stage III colon adenocarcinoma
• No prior chemotherapy
• No prior abdominal or pelvic irradiation
• WHO performance status 0 or 1
• Effective contraception during the study and the following six months
• Signed informed consent obtained prior to any study-specific screening procedures
• Tumour considered as curatively resectable (R0) based on standard preoperative evaluations
• White blood cell count ≥ 3×109/L with neutrophils ≥ 1.5×109/L, platelet count ≥ 100×109/L, haemoglobin ≥ 9 g/dL (5.6 mmol/L)
• Direct bilirubin ≤ 1.5×ULN; ASAT and ALAT ≤ 2.5×ULN; Alkaline phosphatase ≤ 2.5×ULN; Serum creatinine ≤ 1.5×ULN

To be assessed after surgery:

• Delay between diagnosis and first PET/CT < 6 weeks (< 4 weeks recommended).
• Blood glucose < 150 mg/dl at the time of FDG administration. Insulin or oral anti-diabetic medication is not allowed on the days of PET/CT imaging.
• Compliance to the first chemotherapy course to be administered before surgery
• Delay between the first PET/CT imaging and the start of neoadjuvant FOLOFX < 7 days
• Second PET/CT imaging performed on D14 (range: D13-D15, with D0 as the first day of chemo administration)
• Delay between the second PET/CT and surgery < 7 days
• Stage III (ypTNM) as assessed after surgery
• CEA < 1.5 x ULN 1 month after surgery

• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to screening. Incompletely healed wounds or anticipation of the need for major surgical procedure during the course of the study
• Any suspicion of metastatic disease
• Rectal cancer located within 15 cm from the anal verge by endoscopy or under the peritoneal reflection at surgery
• Inflammatory bowel disease
• Pregnancy (absence to be confirmed by ß-hCG blood test) or breast-feeding
• History or current central nervous system disease or peripheral neuropathy
• Hypersensitivity to any of the components of study treatments
• Previous malignancy in the last five years except basal-cell carcinoma of the skin or in situ cervical carcinoma
• Clinically relevant coronary artery disease or history of myocardial infarction in the last 6 weeks or high risk of uncontrolled arrhythmia
• Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent
• Any significant disease which, in the investigator’s opinion, would exclude the patient from the study

FOLFOX : regimen is under the PI’s discretion

Recruitment of first patient: November 15, 2009

Currently 239 out of 240 patients have been recruited

First results expected in 2020

Institut Jules Bordet - ULB

BGDO

1. Institut Jules Bordet
2. AZ Turnhout
3. Hôpital Erasme
4. UCL St-Luc
5. AZ Damiaan
6. AZ Groeninge
7. CHC St-Joseph
8. Clinique St-Bouge
9. UZ Gent
10. Mont-Godinne
11. UZA
12. Brugmann
13. Ambroise Paré
14. CH Jolimont
15. Centre Hospitalier des Ardennes
16. IRIS Etterbeek-Ixelles
17. CHR Citadelle
18. ZNA Stuyvenberg
19. ZNA Middelheim
20. CHR Namur
21. CHU Liège
22. RMHS Baudour