PROTEORECTUM: Proteomic Approach Using Matrix-assisted Laser Desorption/Ionization Tandem Time-of-flight (MALDI-TOF/TOF) of Tumor Response in Rectal Carcinoma After Radiochemotherapy
Sponsor
University Hospital, Bordeaux (Other)
Overall Status
Completed
CT.gov ID
NCT00855946
Collaborator
(none)
46
1
36
1.3
Study Details
Study Description
Brief Summary
Treatment for locally-advanced rectal adenocarcinoma includes preoperative radiochemotherapy before surgery with total mesorectal excision in order to reduce tumor infiltration, facilitate oncologic surgery and improve survival. About fifty percent of these patients are good responders i.e. their tumor infiltration reduces in the rectal wall and regional lymph nodes in order to be graded ypT0 to T2 N0 after pathologic assessment (so called downstaging). At the opposite, bad responders (ypT3-4 and/or N+) are not sensitive to standard preoperative radiochemotherapy, and their survival is poor than good responders. Until now, response to preoperative radiochemotherapy cannot be anticipated before pathological assessment of surgical specimen. Proteomic analysis of sera from good and bad responders to preoperative radiochemotherapy could allow identification of early biomarkers of tumor response, and subsequently adaptation of treatment to increase preoperative treatment efficiency and survival in most patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Good or bad responders to preoperative radiochemotherapy for locally-advanced rectal adenocarcinoma cannot be anticipated before pathological assessment of rectal specimen. The purpose of this prospective monocentric study is to look for early seric biomarkers predictive of tumor response (good and bad responders) in patients treated by preoperative radiochemotherapy (45 Gy) for rectal adenocarcinoma using a proteomic approach. All patients with locally-advanced rectal adenocarcinoma will be enrolled. Sequential samples of sera will be collected before, during preoperative treatment and before surgery, and analysed using a MALDI-TOF-TOF method. Proteomic analysis will be correlated to pathological response in order to identify potential early biomarkers of tumor response.
Study Design
Study Type:
Observational
Actual Enrollment
:
46 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Proteomic Approach Using Matrix-assisted Laser Desorption/Ionization Tandem Time-of-flight (MALDI-TOF/TOF) of Tumor Response in Rectal Carcinoma After Radiochemotherapy
Study Start Date
:
May 1, 2009
Actual Primary Completion Date
:
May 1, 2012
Actual Study Completion Date
:
May 1, 2012
Outcome Measures
Primary Outcome Measures
- differential expression of early seric biomarkers between good and bad responders. [at inclusion and 24-48h after starting radiochemotherapy]
Secondary Outcome Measures
- modifications of isolated biomarkers within presurgical period [at inclusion, 24-48h after initiation of radiochemotherapy, at the end of radiochemotherapy (6th week) and before surgery]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
T3T4 or N+ M0 rectal carcinoma
-
histologically-proven adenocarcinoma
-
from 0 to 15 cm from the anal verge
-
patient is at least 18 years of age
-
ECOG performance status </= 2
-
Patient and doctor have signed informed consent
Exclusion Criteria:
-
Metastatic disease
-
T1-T2 N0 rectal carcinoma
-
Contra indication of radiotherapy or chemotherapy
-
History of cancer
-
Severe renal insufficiency
-
Symptomatic cardiac or coronary insufficiency
-
Patient included in a trial
-
Previous radiotherapy or chemotherapy for this cancer
-
No contraceptive treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Laboratoire d'anatomie pathologique, University Hospital, Bordeaux | Bordeaux | France | 33076 |
Sponsors and Collaborators
- University Hospital, Bordeaux
Investigators
- Principal Investigator: Anne RULLIER, MD, University Hospital Bordeaux, France
- Study Chair: Paul PEREZ, MD, University Hospital Bordeaux, France
Study Documents (Full-Text)
None provided.More Information
Publications
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- Collette L, Bosset JF, den Dulk M, Nguyen F, Mineur L, Maingon P, Radosevic-Jelic L, Piérart M, Calais G; European Organisation for Research and Treatment of Cancer Radiation Oncology Group. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol. 2007 Oct 1;25(28):4379-86.
- García-Aguilar J, Hernandez de Anda E, Sirivongs P, Lee SH, Madoff RD, Rothenberger DA. A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum. 2003 Mar;46(3):298-304.
- Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5.
- Ghadimi BM, Grade M, Difilippantonio MJ, Varma S, Simon R, Montagna C, Füzesi L, Langer C, Becker H, Liersch T, Ried T. Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J Clin Oncol. 2005 Mar 20;23(9):1826-38.
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- Günther K, Dimmler A, Rödel F, Reulbach U, Merkel S, Bittorf BR, Matzel KE, Papadopoulos T, Hohenberger W, Sauer R, Rödel C. P27 does not predict histopathological response to radiochemotherapy in rectal cancer. J Surg Res. 2003 Aug;113(2):179-88.
- Habr-Gama A, Perez RO, Nadalin W, Nahas SC, Ribeiro U Jr, Silva E Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg. 2005 Jan;9(1):90-9; discussion 99-101.
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- Hudelist G, Singer CF, Pischinger KI, Kaserer K, Manavi M, Kubista E, Czerwenka KF. Proteomic analysis in human breast cancer: identification of a characteristic protein expression profile of malignant breast epithelium. Proteomics. 2006 Mar;6(6):1989-2002.
- Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46.
- Komuro Y, Watanabe T, Hosoi Y, Matsumoto Y, Nakagawa K, Tsuno N, Kazama S, Kitayama J, Suzuki N, Nagawa H. The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer. 2002 Sep 15;95(6):1199-205.
- Komuro Y, Watanabe T, Tsurita G, Muto T, Nagawa H. Evaluating the combination of molecular prognostic factors in tumor radiosensitivity in rectal cancer. Hepatogastroenterology. 2005 May-Jun;52(63):666-71.
- Le Moguen K, Lincet H, Marcelo P, Lemoisson E, Heutte N, Duval M, Poulain L, Vinh J, Gauduchon P, Baudin B. A proteomic kinetic analysis of IGROV1 ovarian carcinoma cell line response to cisplatin treatment. Proteomics. 2007 Nov;7(22):4090-101.
- Lopez-Crapez E, Bibeau F, Thézenas S, Ychou M, Simony-Lafontaine J, Thirion A, Azria D, Grenier J, Senesse P. p53 status and response to radiotherapy in rectal cancer: a prospective multilevel analysis. Br J Cancer. 2005 Jun 20;92(12):2114-21.
- Milas L, Mason KA, Ariga H, Hunter N, Neal R, Valdecanas D, Krieg AM, Whisnant JK. CpG oligodeoxynucleotide enhances tumor response to radiation. Cancer Res. 2004 Aug 1;64(15):5074-7.
- Moore HG, Gittleman AE, Minsky BD, Wong D, Paty PB, Weiser M, Temple L, Saltz L, Shia J, Guillem JG. Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Dis Colon Rectum. 2004 Mar;47(3):279-86.
- Murata A, Brown CJ, Raval M, Phang PT. Impact of short-course radiotherapy and low anterior resection on quality of life and bowel function in primary rectal cancer. Am J Surg. 2008 May;195(5):611-5; discussion 615. doi: 10.1016/j.amjsurg.2007.12.034.
- Påhlman L, Glimelius B. Radiotherapy additional to surgery in the management of primary rectal carcinoma. Acta Chir Scand. 1990 Jun-Jul;156(6-7):475-85. Review.
- Peeters KC, van de Velde CJ, Leer JW, Martijn H, Junggeburt JM, Kranenbarg EK, Steup WH, Wiggers T, Rutten HJ, Marijnen CA. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients--a Dutch colorectal cancer group study. J Clin Oncol. 2005 Sep 1;23(25):6199-206.
- Pollack J, Holm T, Cedermark B, Holmström B, Mellgren A. Long-term effect of preoperative radiation therapy on anorectal function. Dis Colon Rectum. 2006 Mar;49(3):345-52.
- Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Medical Research Council Rectal Cancer Working Party. Lancet. 1996 Dec 14;348(9042):1605-10.
- Rau B, Sturm I, Lage H, Berger S, Schneider U, Hauptmann S, Wust P, Riess H, Schlag PM, Dörken B, Daniel PT. Dynamic expression profile of p21WAF1/CIP1 and Ki-67 predicts survival in rectal carcinoma treated with preoperative radiochemotherapy. J Clin Oncol. 2003 Sep 15;21(18):3391-401. Epub 2003 Jul 28. Erratum in: J Clin Oncol. 2004 Feb 1;22(3):576.
- Rödel C, Grabenbauer GG, Papadopoulos T, Bigalke M, Günther K, Schick C, Peters A, Sauer R, Rödel F. Apoptosis as a cellular predictor for histopathologic response to neoadjuvant radiochemotherapy in patients with rectal cancer. Int J Radiat Oncol Biol Phys. 2002 Feb 1;52(2):294-303.
- Rödel C, Martus P, Papadoupolos T, Füzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005 Dec 1;23(34):8688-96. Epub 2005 Oct 24.
- Rödel F, Hoffmann J, Distel L, Herrmann M, Noisternig T, Papadopoulos T, Sauer R, Rödel C. Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res. 2005 Jun 1;65(11):4881-7.
- Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40.
- Smith FM, Gallagher WM, Fox E, Stephens RB, Rexhepaj E, Petricoin EF 3rd, Liotta L, Kennedy MJ, Reynolds JV. Combination of SELDI-TOF-MS and data mining provides early-stage response prediction for rectal tumors undergoing multimodal neoadjuvant therapy. Ann Surg. 2007 Feb;245(2):259-66.
- Smith FM, Reynolds JV, Kay EW, Crotty P, Murphy JO, Hollywood D, Gaffney EF, Stephens RB, Kennedy MJ. COX-2 overexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy. Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):466-72. Epub 2005 Oct 5.
- Smith FM, Reynolds JV, Miller N, Stephens RB, Kennedy MJ. Pathological and molecular predictors of the response of rectal cancer to neoadjuvant radiochemotherapy. Eur J Surg Oncol. 2006 Feb;32(1):55-64. Epub 2005 Dec 1. Review.
- Swedish Rectal Cancer Trial, Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997 Apr 3;336(14):980-7. Erratum in: N Engl J Med 1997 May 22;336(21):1539.
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Responsible Party:
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT00855946
Other Study ID Numbers:
- CHUBX - 2008/25
First Posted:
Mar 5, 2009
Last Update Posted:
May 9, 2013
Last Verified:
May 1, 2013
Keywords provided by University Hospital, Bordeaux
Additional relevant MeSH terms: