Preoperative Chemosensitivity Testing to Predict Treatment Benefit in Adjuvant Stage III Colon Cancer (PePiTA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Jules Bordet Institute
Sponsor:
Information provided by (Responsible Party):
Jules Bordet Institute
ClinicalTrials.gov Identifier:
NCT00994864
First received: October 13, 2009
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

The primary working hypothesis is that preoperative chemo-sensitivity testing using fluorodeoxyglucose positron emission tomography (FDG-PET) performed before and after one course of FOLFOX (folinic acid, fluorouracil, oxaliplatin) can identify the patients that will least likely have a significant benefit from adjuvant FOLFOX for stage III colon cancer. The benefit will be analyzed by correlating the preoperative FDG-PET uptake changes to the disease free and overall survival.


Condition Intervention
Colon Cancer
Drug: FOLFOX

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Preoperative Chemosensitivity Testing as Predictor of Treatment Benefit in Adjuvant Stage III Colon Cancer: PePiTA Trial

Resource links provided by NLM:


Further study details as provided by Jules Bordet Institute:

Primary Outcome Measures:
  • 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. [ Time Frame: Within 3 years after completion of adjuvant chemotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Examine the predictive value of PET-assessed tumour FDG uptake changes after one course of preoperative chemotherapy on OS [ Time Frame: Within 3 years after completion of adjuvant chemotherapy ] [ Designated as safety issue: No ]
  • Evaluate the best cut-off value for relative delta SUV in assessment of preoperative chemotherapy response by FDG-PET/CT imaging. [ Time Frame: Within 3 years after completion of adjuvant chemotherapy ] [ Designated as safety issue: No ]
  • Analyze the cost-effectiveness of preoperative chemo-sensitivity testing [ Time Frame: Within 3 years after completion of adjuvant chemotherapy ] [ Designated as safety issue: No ]
  • Assess the predictive value of circulating tumour cells on disease-free survival [ Time Frame: Within 3 years after completion of adjuvant chemotherapy ] [ Designated as safety issue: No ]
  • Assess the predictive value of SNPs on toxicity- and drug target-related genes on DFS [ Time Frame: Within 3 years after completion of adjuvant chemotherapy ] [ Designated as safety issue: Yes ]
  • Create a frozen tumour bank for future studies [ Time Frame: Within 2 years from the beginning of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 135
Study Start Date: November 2009
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
adjuvant FOLFOX (1 pre-operative cycle)
One cycle of preoperative standard FOLFOX chemotherapy followed by eleven cycles post-operatively. PET/CT before and after the pre-operative chemotherapy cycle.
Drug: FOLFOX
One cycle of standard FOLFOX pre-operatively followed by 11 cycles of standard adjuvant FOLFOX chemotherapy.
Other Name: FOLFOX-4 or equivalent

Detailed Description:

Patients with histological confirmed colon adenocarcinoma compatible with clinical stage II or III are eligible for study screening. Receipt of a signed informed consent and study inclusion should be done within 15 days after histological diagnosis. A usual workup for preoperative staging of colon cancer must be done not more than 1 month before study inclusion and include CEA assessment, positive histological sample for colon adenocarcinoma and chest and abdominal CT scan. After receipt of the written consent, the patient undergoes baseline PET/CT scan and donates blood samples for CTC and SNP analyses. Delay between baseline examinations and histological diagnosis must not exceed 21 days. The baseline examinations should be done within 1 week before beginning of the first course of FOLFOX chemotherapy. Thirteen to 15 days after chemotherapy, the PET/CT and blood sampling for CTC analysis are repeated. Standard surgery follows after 15 days but no more than 30 days from Day 1 of preoperative chemotherapy. Two frozen tissue cores are obtained during surgery and sent immediately in dry ice shipping to the central Tumour Bank (Jules Bordet Institute) or stored locally at -80°C to be sent in batches to the central tumour bank. Thereafter, the patient receives standard care, according to tumour pathological stage. In fully eligible patients, FOLFOX chemotherapy should be started not more than 45 days after surgery. In stage III patients otherwise ineligible, recommendation is to start FOLFOX chemotherapy within 45 days after surgery although such patients will not be included in the primary analysis. Treatment in case of stage II or stage IV colon cancer is left at investigator's discretion. Eleven courses of adjuvant FOLFOX are foreseen, in order to match the usual recommendation coming from the Mosaic Trial.

Follow-up procedures after completion of adjuvant treatment will follow standard European clinical recommendations for stage II and III patients. Clinical follow-up data will be obtained for all patients, including those with stage II disease, with a minimum follow-up time of three years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Delay between assessment of screening criteria and first PET/CT < 21 days
  • 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 D1 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 -

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00994864

Contacts
Contact: Alain Hendlisz, MD 2 5413541 ext 0032 alain.hendlisz@bordet.be
Contact: Anne Denis 2 5413196 ext 0032 anne.denis@bordet.be

Locations
Belgium
ZNA Stuivenberg Recruiting
Antwerpen, Belgium, 2060
Contact: Michael Fried, MD       michael.fried@zna.be   
Principal Investigator: Michael Fried, MD         
ZNA - Middelheim Recruiting
Antwerpen, Belgium, 2020
Contact: Dirk Schrivers, MD         
Principal Investigator: Dirk Schrivers, MD         
Clinique St-Luc Bouge Recruiting
Bouge, Belgium, 5004
Contact: Marylene Clausse, MD       marylene.clausse@ct-luc-bouge.be   
Principal Investigator: Marylene Clausse, MD         
CHU Brugmann Recruiting
Brussels, Belgium, 1020
Contact: André Efira, MD       andre.efira@chu-brugmann.be   
Principal Investigator: André Efira, MD         
Clin Université St-Luc Bruxelles Recruiting
Brussels, Belgium, 1200
Contact: Yves Humblet, MD       yves.humblet@uclouvain.be   
Principal Investigator: Yves Humblet, MD         
Jules Bordet Institute Recruiting
Brussels, Belgium, 1000
Contact: Alain Hendlisz, MD       alain.hendlisz@bordet.be   
Contact: Anne Denis       anne.denis@bordet.be   
Principal Investigator: Alain Hendlisz, MD         
Hôpital Erasme Recruiting
Brussels, Belgium, 1000
Contact: Jean-Luc Van Laethem, MD       jl.vanlaethem@erasme.ulb.ac.be   
Principal Investigator: Jean-Luc Van Laethem, MD         
IRIS Etterbeek-Ixelles Recruiting
Brussels, Belgium, 1050
Contact: Jean-Pierre Kains, MD       jpkains@his.irisnet.be   
Principal Investigator: Jean-Pierre Kains, MD         
UZ Antwerp Recruiting
Edegem, Belgium, 2650
Contact: Marc Peeters, MD       marc.peeters@ugent.be   
Principal Investigator: Marc Peeters, MD         
UZ Gent Recruiting
Gent, Belgium, 9000
Contact: Stéphanie Laurent, MD       stephanie.laurent@ugent.be   
Principal Investigator: Stéphanie Laurent, MD         
Centre Hopital Jolimont-Lobbes Recruiting
Haine, St Paul, Belgium, 7100
Contact: Thierry Delaunoit, MD       thierry.delaunoit@entitejolimontoise.be   
Principal Investigator: Thierry Delaunoit, MD         
AZ Groeninge Recruiting
Kortrijk, Belgium, 8500
Contact: Philippe Vergauwe, MD       philippe.vergauwe@azgroeninge.be   
Principal Investigator: Philippe Vergauwe, MD         
Centre Hospitalier des Ardenes Recruiting
Libramont, Belgium, 6800
Contact: Frédérick Forget, MD       frederic.forget@cha.be   
Principal Investigator: Frédérick Forget, MD         
CHR Citadelle de Liege Recruiting
Liege, Belgium, 4000
Contact: Bernard Delhougne, MD       nathalie.coeurnelle@chrcitadelle.be   
Principal Investigator: Bernard Delhougne, MD         
CHU De Liège Recruiting
Liège, Belgium, 4000
Contact: Marc Polus, MD       marc.polus@skynet.be   
Principal Investigator: Marc Polus, MD         
Clinique St-Joseph Recruiting
Liège, Belgium, 4000
Contact: Gauthier Demolin       gauthier.demolin@chc.be   
Principal Investigator: Gauthier Demolin, MD         
ZNA - Jan Palfijin Recruiting
Merksem, Belgium, 2170
Contact: Joanna Vermeij, MD         
Principal Investigator: Joanna Vermeij, MD         
CHR Namur Recruiting
Namur, Belgium, 5000
Contact: Thierry De Grez, MD       thierry.degrez@chrnamur.be   
Principal Investigator: Thierry De Grez, MD         
AZ Damiaan Recruiting
Oostende, Belgium, 8400
Contact: Guido Deboever, MD       gdeboever@azdamiaan.be   
Principal Investigator: Guido Deboever, MD         
clinique St Pierre Ottignies Recruiting
Ottignies, Belgium
Clinique Universites UCL Mont-Godinne Recruiting
Yvoir, Belgium, 5530
Contact: Joseph Kerger, MD       joseph.kerger@sang.ucl.ac.be   
Principal Investigator: Joseph Kerger, MD         
Sponsors and Collaborators
Jules Bordet Institute
Investigators
Principal Investigator: Alain Hendlisz, MD Jules Bordet Institute, Brussels, Belgium
  More Information

No publications provided

Responsible Party: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT00994864     History of Changes
Other Study ID Numbers: PEPITA 001, EudraCT number: 2009-011445-13
Study First Received: October 13, 2009
Last Updated: March 10, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board
Belgium: Ministry of Social Affairs, Public Health and the Environment

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on September 22, 2014