search
Back to results

Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Bevacizumab With FOLFOX or FOLFIRI. (BEV-ONCO2012)

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Metastases resection
Bevacizumab
5 FU
Oxaliplatin
Irinotecan
Sponsored by
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring metastatic, colorectal, cancer, liver, Bevacizumab, Pathological response

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 1. Female or male patients with at least 18 years at the time the informed consent is signed
  • 2.ECOG (Eastern Cooperative Oncology Group)performance status 0 or 1
  • 3.Histological or cytological confirmed diagnostic of adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Wild-type or mutated KRAS tumor status.
  • 4.Patients must present a resectable metastatic disease for which the decision of preoperative chemotherapy is considered. Resectability could be planned in one or multiple stage if indicated. As commonly admitted, resectability means the surgical clearance (+/- radiofrequency ablation) of all detectable (liver) lesions with tumor-free margins and compatible with an adequate hepatic reserve. Practically, bilateral tumor location, number and location of lesions, and inadequate hepatic reserve remain the main decisional factors.
  • 5.Partial and minor resection of metastatic disease is allowed within 3 months before inclusion if patient has never received chemotherapy for mCRC.
  • 6.Extra hepatic metastatic location is limited to 1 site. Extra-hepatic location must be easily resectable in one stage surgery.
  • 7.Patients may have received adjuvant chemotherapy or (neo-) adjuvant chemo-radiotherapy to the pelvis, provided the last dose of chemotherapy was administered at least 6 months prior to inclusion (12 months for oxaliplatin). Previous radiotherapy to the pelvis is not an exclusion criterion.
  • 8.Adequate haematological, renal and hepatic function as follows: Haematological Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L Renal Creatinine < 1.5 x ULN (Upper Limit of Normal) Hepatic Bilirubin < 1.5 X ULN AST(Aspartate aminotransferase), ALT (Alanine Aminotransferase) < 5 x ULN Phos Alc. < 5 x ULN
  • 9.Proteinuria <2+ (dipstick urinalysis) or =1g/24hour.
  • 10.No history of myocardial infarction and/or stroke within 6 months prior to randomization. No uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy.
  • 11.Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception.
  • 12.Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception.
  • 13.Life expectancy of at least 3 months without any active treatment.

Exclusion Criteria:

  • 1.Non resectable mCRC (metastatic ColoRectal Cancer) (if resectability remains uncertain or unprobable after 3 months chemotherapy, patient is excluded from the trial).
  • 2.Prior chemotherapy or systemic therapy for mCRC. Adjuvant chemotherapy for colorectal cancer is not an exclusion criterion provided that it was completed more than 6 months prior to inclusion. Oxaliplatin-based chemotherapy must be completed more than 1 year prior to inclusion.
  • 3.Prior utilization of bevacizumab, aflibercept (or other anti-VEGF(vascular endothelial growth factor) therapy).
  • 4.Previous radiotherapy delivered to the upper abdomen.
  • 5.Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiologic assessment.
  • 6.Prior major liver resection: remnant liver < 50% of the initial liver volume.
  • 7.Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.
  • 8.Concurrent central nervous systems metastases
  • 9.Peripheric neuropathy ≥ grade 2.
  • 10.Interstitial lung disease
  • 11.Pregnant or breast feeding.
  • 12.The patient has previous or concomitant malignancies, except: Invasive malignancies in remission for more than 5 years and non melanoma skin cancer or carcinoma in situ of the cervix.

Sites / Locations

  • Clinique Saint Luc
  • CHIREC
  • Cliniques universitaires Saint-Luc
  • Grand Hopital de Charleroi
  • AZ Groeninge
  • Centre Hospitalier Jolimont Lobbes
  • CHC Liège clinique Saint Joseph
  • CHU liège (Sart Timan)
  • Clinique Maternité Saint Elisabeth
  • Clinique Saint Pierre Ottignies
  • CHU-UCL Dinant-Godinne

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Folfox: oxaliplatin +leucovorin+ 5FU

FOLFIRI: irinotecan+leucovorin+5FU

Arm Description

FOLFOX (oxaliplatin +leucovorin+ 5FU) +bevacizumab+ metastases resection

FOLFIRI (irinotecan+leucovorin+5FU) +bevacizumab +metastases resection

Outcomes

Primary Outcome Measures

the major pathological response rate
This is at the surgery time. The metastases resection must be process after 6 cycles of randomized chemotherapy + target therapy. It depend but it will be normally 3 months after patient inclusion in the study

Secondary Outcome Measures

Progression free survival
Overall Survival
The overall survival will be analyzed at the end of the study (3 years of recruitment and one years of follow-up)
Clinical Response Rate
Metabolic Response Rate
Post operative complication

Full Information

First Posted
May 7, 2013
Last Updated
October 20, 2020
Sponsor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Collaborators
Grand Hôpital de Charleroi
search

1. Study Identification

Unique Protocol Identification Number
NCT01858649
Brief Title
Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Bevacizumab With FOLFOX or FOLFIRI.
Acronym
BEV-ONCO2012
Official Title
Randomized Phase 2 Study Comparing Pathological Responses on Colorectal Cancer Metastases After Preoperative Treatment Combining Bevacizumab With FOLFOX or FOLFIRI
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
May 2013 (Actual)
Primary Completion Date
May 2019 (Actual)
Study Completion Date
May 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Collaborators
Grand Hôpital de Charleroi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study is designed to analyze the pathological tumor response on resected colorectal cancer metastases after preoperative treatment with bevacizumab combined with FOLFOX or FOLFIRI regimen in a prospective cohort and to correlate this response with patient's outcome.
Detailed Description
This is a phase II , openlabel, randomized study in patients with confirmed diagnosis of resectable metastatic colorectal adenocarcinoma , who have not received prior chemotherapy for their metastatic disease. The study is designed to compare pathological responses observed after pre-operative chemotherapy bevacizumab with FOLFOX or FOLFIRI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
metastatic, colorectal, cancer, liver, Bevacizumab, Pathological response

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Folfox: oxaliplatin +leucovorin+ 5FU
Arm Type
Active Comparator
Arm Description
FOLFOX (oxaliplatin +leucovorin+ 5FU) +bevacizumab+ metastases resection
Arm Title
FOLFIRI: irinotecan+leucovorin+5FU
Arm Type
Active Comparator
Arm Description
FOLFIRI (irinotecan+leucovorin+5FU) +bevacizumab +metastases resection
Intervention Type
Procedure
Intervention Name(s)
Metastases resection
Intervention Description
Surgery of colorectal cancer metastases will be proceeded after 3 to 6 cycles of chemotherapy ( folfox or folfiri) + bevacizumab .
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab 5 mg/kg in 100 ml NaCl 0.9% IV infusion 3 to 5 cycles. No bevacizumab for ultimate cycle .
Intervention Type
Drug
Intervention Name(s)
5 FU
Other Intervention Name(s)
5-Fluorouracile
Intervention Description
Leucovorin L (levoleucovorin) 200 mg/m2 (or folinic acid 400 mg/m²) in 250 ml glucose 5%, IV infusion 3 to 6 cycles 5-FU bolus 400 mg/m2, IV bolus 3 to 6 cycles 5-FU continuous infusion 2400 mg/m2, 46-hour cont. IV infusion 3 to 6 cycles
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
oxaliplatin 85 mg/m² in 150 ml NaCl 0.9%, IV infusion 3 to 6 cycles
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Campto, Irinosin
Intervention Description
Irinotecan 180 mg/m² in 150 ml NaCl 0.9%, IV infusion 3 to 6 cycles
Primary Outcome Measure Information:
Title
the major pathological response rate
Description
This is at the surgery time. The metastases resection must be process after 6 cycles of randomized chemotherapy + target therapy. It depend but it will be normally 3 months after patient inclusion in the study
Time Frame
After surgery (Metastases resection-average 3 months)
Secondary Outcome Measure Information:
Title
Progression free survival
Time Frame
at 6 months and at 12 months after randomization
Title
Overall Survival
Description
The overall survival will be analyzed at the end of the study (3 years of recruitment and one years of follow-up)
Time Frame
At the end of the study
Title
Clinical Response Rate
Time Frame
At time of surgery - average 3 months
Title
Metabolic Response Rate
Time Frame
At time of surgery - Average 3 months
Title
Post operative complication
Time Frame
One month after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Female or male patients with at least 18 years at the time the informed consent is signed 2.ECOG (Eastern Cooperative Oncology Group)performance status 0 or 1 3.Histological or cytological confirmed diagnostic of adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Wild-type or mutated KRAS tumor status. 4.Patients must present a resectable metastatic disease for which the decision of preoperative chemotherapy is considered. Resectability could be planned in one or multiple stage if indicated. As commonly admitted, resectability means the surgical clearance (+/- radiofrequency ablation) of all detectable (liver) lesions with tumor-free margins and compatible with an adequate hepatic reserve. Practically, bilateral tumor location, number and location of lesions, and inadequate hepatic reserve remain the main decisional factors. 5.Partial and minor resection of metastatic disease is allowed within 3 months before inclusion if patient has never received chemotherapy for mCRC. 6.Extra hepatic metastatic location is limited to 1 site. Extra-hepatic location must be easily resectable in one stage surgery. 7.Patients may have received adjuvant chemotherapy or (neo-) adjuvant chemo-radiotherapy to the pelvis, provided the last dose of chemotherapy was administered at least 6 months prior to inclusion (12 months for oxaliplatin). Previous radiotherapy to the pelvis is not an exclusion criterion. 8.Adequate haematological, renal and hepatic function as follows: Haematological Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L Renal Creatinine < 1.5 x ULN (Upper Limit of Normal) Hepatic Bilirubin < 1.5 X ULN AST(Aspartate aminotransferase), ALT (Alanine Aminotransferase) < 5 x ULN Phos Alc. < 5 x ULN 9.Proteinuria <2+ (dipstick urinalysis) or =1g/24hour. 10.No history of myocardial infarction and/or stroke within 6 months prior to randomization. No uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy. 11.Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception. 12.Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception. 13.Life expectancy of at least 3 months without any active treatment. Exclusion Criteria: 1.Non resectable mCRC (metastatic ColoRectal Cancer) (if resectability remains uncertain or unprobable after 3 months chemotherapy, patient is excluded from the trial). 2.Prior chemotherapy or systemic therapy for mCRC. Adjuvant chemotherapy for colorectal cancer is not an exclusion criterion provided that it was completed more than 6 months prior to inclusion. Oxaliplatin-based chemotherapy must be completed more than 1 year prior to inclusion. 3.Prior utilization of bevacizumab, aflibercept (or other anti-VEGF(vascular endothelial growth factor) therapy). 4.Previous radiotherapy delivered to the upper abdomen. 5.Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiologic assessment. 6.Prior major liver resection: remnant liver < 50% of the initial liver volume. 7.Non-malignant disease that would render the patient unsuitable for treatment according to this protocol. 8.Concurrent central nervous systems metastases 9.Peripheric neuropathy ≥ grade 2. 10.Interstitial lung disease 11.Pregnant or breast feeding. 12.The patient has previous or concomitant malignancies, except: Invasive malignancies in remission for more than 5 years and non melanoma skin cancer or carcinoma in situ of the cervix.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Van den Eynde, MD
Organizational Affiliation
Cliniques universitaires Saint-Luc
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Javier Carrasco, MD PhD
Organizational Affiliation
Grand Hôpital de Charleroi - Notre-Dame
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinique Saint Luc
City
Bouge
ZIP/Postal Code
5004
Country
Belgium
Facility Name
CHIREC
City
Brussels
ZIP/Postal Code
1180
Country
Belgium
Facility Name
Cliniques universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Grand Hopital de Charleroi
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
AZ Groeninge
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
Facility Name
Centre Hospitalier Jolimont Lobbes
City
La Louvière
ZIP/Postal Code
7100
Country
Belgium
Facility Name
CHC Liège clinique Saint Joseph
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
CHU liège (Sart Timan)
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Clinique Maternité Saint Elisabeth
City
Namur
ZIP/Postal Code
5000
Country
Belgium
Facility Name
Clinique Saint Pierre Ottignies
City
Ottignies
ZIP/Postal Code
1340
Country
Belgium
Facility Name
CHU-UCL Dinant-Godinne
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium

12. IPD Sharing Statement

Citations:
PubMed Identifier
19474385
Citation
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.
Results Reference
background
PubMed Identifier
9161393
Citation
Jamison RL, Donohue JH, Nagorney DM, Rosen CB, Harmsen WS, Ilstrup DM. Hepatic resection for metastatic colorectal cancer results in cure for some patients. Arch Surg. 1997 May;132(5):505-10; discussion 511. doi: 10.1001/archsurg.1997.01430290051008.
Results Reference
background
PubMed Identifier
8608500
Citation
Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, Jaeck D. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer. 1996 Apr 1;77(7):1254-62.
Results Reference
background
PubMed Identifier
18156932
Citation
Rees M, Tekkis PP, Welsh FK, O'Rourke T, John TG. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008 Jan;247(1):125-35. doi: 10.1097/SLA.0b013e31815aa2c2.
Results Reference
background
PubMed Identifier
18358928
Citation
Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T; EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Federation Francophone de Cancerologie Digestive (FFCD). Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008 Mar 22;371(9617):1007-16. doi: 10.1016/S0140-6736(08)60455-9.
Results Reference
background
PubMed Identifier
15175435
Citation
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42. doi: 10.1056/NEJMoa032691.
Results Reference
background
PubMed Identifier
18421054
Citation
Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008 Apr 20;26(12):2013-9. doi: 10.1200/JCO.2007.14.9930. Erratum In: J Clin Oncol. 2008 Jun;26(18):3110. J Clin Oncol. 2009 Feb 1;27(4):653.
Results Reference
background
PubMed Identifier
21502544
Citation
Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. doi: 10.1200/JCO.2010.33.5091. Epub 2011 Apr 18.
Results Reference
background
PubMed Identifier
22446022
Citation
Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Kohne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. doi: 10.1016/j.ejca.2012.02.057. Epub 2012 Mar 23.
Results Reference
background
PubMed Identifier
20921465
Citation
Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4.
Results Reference
background
PubMed Identifier
17532622
Citation
Khatri VP, Chee KG, Petrelli NJ. Modern multimodality approach to hepatic colorectal metastases: solutions and controversies. Surg Oncol. 2007 Jul;16(1):71-83. doi: 10.1016/j.suronc.2007.05.001. Epub 2007 May 29.
Results Reference
background
PubMed Identifier
17449351
Citation
de Gramont A, Tournigand C, Andre T, Larsen AK, Louvet C. Adjuvant therapy for stage II and III colorectal cancer. Semin Oncol. 2007 Apr;34(2 Suppl 1):S37-40. doi: 10.1053/j.seminoncol.2007.01.004.
Results Reference
background
PubMed Identifier
15175436
Citation
Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004 Jun 3;350(23):2343-51. doi: 10.1056/NEJMoa032709.
Results Reference
background
PubMed Identifier
18398148
Citation
Gruenberger B, Tamandl D, Schueller J, Scheithauer W, Zielinski C, Herbst F, Gruenberger T. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008 Apr 10;26(11):1830-5. doi: 10.1200/JCO.2007.13.7679.
Results Reference
background
PubMed Identifier
20177795
Citation
Klinger M, Tamandl D, Eipeldauer S, Hacker S, Herberger B, Kaczirek K, Dorfmeister M, Gruenberger B, Gruenberger T. Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX. Ann Surg Oncol. 2010 Aug;17(8):2059-65. doi: 10.1245/s10434-010-0972-9. Epub 2010 Feb 23.
Results Reference
background
PubMed Identifier
19942479
Citation
Folprecht G, Gruenberger T, Bechstein WO, Raab HR, Lordick F, Hartmann JT, Lang H, Frilling A, Stoehlmacher J, Weitz J, Konopke R, Stroszczynski C, Liersch T, Ockert D, Herrmann T, Goekkurt E, Parisi F, Kohne CH. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010 Jan;11(1):38-47. doi: 10.1016/S1470-2045(09)70330-4. Epub 2009 Nov 26.
Results Reference
background
PubMed Identifier
17960603
Citation
Ribero D, Wang H, Donadon M, Zorzi D, Thomas MB, Eng C, Chang DZ, Curley SA, Abdalla EK, Ellis LM, Vauthey JN. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer. 2007 Dec 15;110(12):2761-7. doi: 10.1002/cncr.23099.
Results Reference
background
PubMed Identifier
18854565
Citation
Kesmodel SB, Ellis LM, Lin E, Chang GJ, Abdalla EK, Kopetz S, Vauthey JN, Rodriguez-Bigas MA, Curley SA, Feig BW. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol. 2008 Nov 10;26(32):5254-60. doi: 10.1200/JCO.2008.17.7857. Epub 2008 Oct 14.
Results Reference
background
PubMed Identifier
17103075
Citation
D'Angelica M, Kornprat P, Gonen M, Chung KY, Jarnagin WR, DeMatteo RP, Fong Y, Kemeny N, Blumgart LH, Saltz LB. Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched case-control study. Ann Surg Oncol. 2007 Feb;14(2):759-65. doi: 10.1245/s10434-006-9074-0. Epub 2006 Nov 11.
Results Reference
background
PubMed Identifier
18155574
Citation
Reddy SK, Morse MA, Hurwitz HI, Bendell JC, Gan TJ, Hill SE, Clary BM. Addition of bevacizumab to irinotecan- and oxaliplatin-based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg. 2008 Jan;206(1):96-106. doi: 10.1016/j.jamcollsurg.2007.06.290. Epub 2007 Sep 17.
Results Reference
background
PubMed Identifier
19200687
Citation
Klinger M, Eipeldauer S, Hacker S, Herberger B, Tamandl D, Dorfmeister M, Koelblinger C, Gruenberger B, Gruenberger T. Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases. Eur J Surg Oncol. 2009 May;35(5):515-20. doi: 10.1016/j.ejso.2008.12.013. Epub 2009 Feb 5.
Results Reference
background
PubMed Identifier
22552819
Citation
van der Pool AE, Marsman HA, Verheij J, Ten Kate FJ, Eggermont AM, Ijzermans JN, Verhoef C. Effect of bevacizumab added preoperatively to oxaliplatin on liver injury and complications after resection of colorectal liver metastases. J Surg Oncol. 2012 Dec;106(7):892-7. doi: 10.1002/jso.23142. Epub 2012 May 2.
Results Reference
background
PubMed Identifier
8194005
Citation
Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, Jacob JH, Segol P, Samama G, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994 Jun 1;73(11):2680-6. doi: 10.1002/1097-0142(19940601)73:113.0.co;2-c.
Results Reference
background
PubMed Identifier
15849517
Citation
Swisher SG, Hofstetter W, Wu TT, Correa AM, Ajani JA, Komaki RR, Chirieac L, Hunt KK, Liao Z, Phan A, Rice DC, Vaporciyan AA, Walsh GL, Roth JA. Proposed revision of the esophageal cancer staging system to accommodate pathologic response (pP) following preoperative chemoradiation (CRT). Ann Surg. 2005 May;241(5):810-7; discussion 817-20. doi: 10.1097/01.sla.0000161983.82345.85.
Results Reference
background
PubMed Identifier
15718321
Citation
Ajani JA, Mansfield PF, Crane CH, Wu TT, Lunagomez S, Lynch PM, Janjan N, Feig B, Faust J, Yao JC, Nivers R, Morris J, Pisters PW. Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome. J Clin Oncol. 2005 Feb 20;23(6):1237-44. doi: 10.1200/JCO.2005.01.305.
Results Reference
background
PubMed Identifier
16246976
Citation
Rodel C, Martus P, Papadoupolos T, Fuzesi 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. doi: 10.1200/JCO.2005.02.1329. Epub 2005 Oct 24.
Results Reference
background
PubMed Identifier
11920483
Citation
Bouzourene H, Bosman FT, Seelentag W, Matter M, Coucke P. Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer. 2002 Feb 15;94(4):1121-30.
Results Reference
background
PubMed Identifier
17060484
Citation
Rubbia-Brandt L, Giostra E, Brezault C, Roth AD, Andres A, Audard V, Sartoretti P, Dousset B, Majno PE, Soubrane O, Chaussade S, Mentha G, Terris B. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol. 2007 Feb;18(2):299-304. doi: 10.1093/annonc/mdl386. Epub 2006 Oct 23.
Results Reference
background
PubMed Identifier
18936472
Citation
Blazer DG 3rd, Kishi Y, Maru DM, Kopetz S, Chun YS, Overman MJ, Fogelman D, Eng C, Chang DZ, Wang H, Zorzi D, Ribero D, Ellis LM, Glover KY, Wolff RA, Curley SA, Abdalla EK, Vauthey JN. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol. 2008 Nov 20;26(33):5344-51. doi: 10.1200/JCO.2008.17.5299. Epub 2008 Oct 20.
Results Reference
background
PubMed Identifier
20697255
Citation
Maru DM, Kopetz S, Boonsirikamchai P, Agarwal A, Chun YS, Wang H, Abdalla EK, Kaur H, Charnsangavej C, Vauthey JN, Loyer EM. Tumor thickness at the tumor-normal interface: a novel pathologic indicator of chemotherapy response in hepatic colorectal metastases. Am J Surg Pathol. 2010 Sep;34(9):1287-94. doi: 10.1097/PAS.0b013e3181eb2f7b.
Results Reference
background
PubMed Identifier
19097774
Citation
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
Results Reference
background
PubMed Identifier
10673991
Citation
Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999 Dec;35(13):1773-82. doi: 10.1016/s0959-8049(99)00229-4.
Results Reference
background
PubMed Identifier
14998849
Citation
Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004 Mar;15(3):460-6. doi: 10.1093/annonc/mdh095.
Results Reference
background
PubMed Identifier
17008531
Citation
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006 Sep 29;313(5795):1960-4. doi: 10.1126/science.1129139.
Results Reference
background
PubMed Identifier
17332313
Citation
Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res. 2007 Mar 1;67(5):1883-6. doi: 10.1158/0008-5472.CAN-06-4806.
Results Reference
background
PubMed Identifier
21245428
Citation
Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman WH, Pages F, Galon J. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011 Feb 20;29(6):610-8. doi: 10.1200/JCO.2010.30.5425. Epub 2011 Jan 18.
Results Reference
background
PubMed Identifier
16371631
Citation
Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005 Dec 22;353(25):2654-66. doi: 10.1056/NEJMoa051424.
Results Reference
background
PubMed Identifier
19858404
Citation
Pages F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G, Lagorce C, Wind P, Marliot F, Bruneval P, Zatloukal K, Trajanoski Z, Berger A, Fridman WH, Galon J. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol. 2009 Dec 10;27(35):5944-51. doi: 10.1200/JCO.2008.19.6147. Epub 2009 Oct 26.
Results Reference
background
PubMed Identifier
19105846
Citation
Butterfield LH, Disis ML, Fox BA, Lee PP, Khleif SN, Thurin M, Trinchieri G, Wang E, Wigginton J, Chaussabel D, Coukos G, Dhodapkar M, Hakansson L, Janetzki S, Kleen TO, Kirkwood JM, Maccalli C, Maecker H, Maio M, Malyguine A, Masucci G, Palucka AK, Potter DM, Ribas A, Rivoltini L, Schendel D, Seliger B, Selvan S, Slingluff CL Jr, Stroncek DF, Streicher H, Wu X, Zeskind B, Zhao Y, Zocca MB, Zwierzina H, Marincola FM. A systematic approach to biomarker discovery; preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers". J Transl Med. 2008 Dec 23;6:81. doi: 10.1186/1479-5876-6-81.
Results Reference
background
PubMed Identifier
21558394
Citation
Butterfield LH, Palucka AK, Britten CM, Dhodapkar MV, Hakansson L, Janetzki S, Kawakami Y, Kleen TO, Lee PP, Maccalli C, Maecker HT, Maino VC, Maio M, Malyguine A, Masucci G, Pawelec G, Potter DM, Rivoltini L, Salazar LG, Schendel DJ, Slingluff CL Jr, Song W, Stroncek DF, Tahara H, Thurin M, Trinchieri G, van Der Burg SH, Whiteside TL, Wigginton JM, Marincola F, Khleif S, Fox BA, Disis ML. Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers. Clin Cancer Res. 2011 May 15;17(10):3064-76. doi: 10.1158/1078-0432.CCR-10-2234. Epub 2011 May 10.
Results Reference
background
PubMed Identifier
19534815
Citation
Tahara H, Sato M, Thurin M, Wang E, Butterfield LH, Disis ML, Fox BA, Lee PP, Khleif SN, Wigginton JM, Ambs S, Akutsu Y, Chaussabel D, Doki Y, Eremin O, Fridman WH, Hirohashi Y, Imai K, Jacobson J, Jinushi M, Kanamoto A, Kashani-Sabet M, Kato K, Kawakami Y, Kirkwood JM, Kleen TO, Lehmann PV, Liotta L, Lotze MT, Maio M, Malyguine A, Masucci G, Matsubara H, Mayrand-Chung S, Nakamura K, Nishikawa H, Palucka AK, Petricoin EF, Pos Z, Ribas A, Rivoltini L, Sato N, Shiku H, Slingluff CL, Streicher H, Stroncek DF, Takeuchi H, Toyota M, Wada H, Wu X, Wulfkuhle J, Yaguchi T, Zeskind B, Zhao Y, Zocca MB, Marincola FM. Emerging concepts in biomarker discovery; the US-Japan Workshop on Immunological Molecular Markers in Oncology. J Transl Med. 2009 Jun 17;7:45. doi: 10.1186/1479-5876-7-45.
Results Reference
background
PubMed Identifier
20207124
Citation
Bindea G, Mlecnik B, Fridman WH, Pages F, Galon J. Natural immunity to cancer in humans. Curr Opin Immunol. 2010 Apr;22(2):215-22. doi: 10.1016/j.coi.2010.02.006. Epub 2010 Mar 6.
Results Reference
background
PubMed Identifier
19946335
Citation
Pages F, Galon J, Dieu-Nosjean MC, Tartour E, Sautes-Fridman C, Fridman WH. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene. 2010 Feb 25;29(8):1093-102. doi: 10.1038/onc.2009.416. Epub 2009 Nov 30.
Results Reference
background
PubMed Identifier
21245434
Citation
Broussard EK, Disis ML. TNM staging in colorectal cancer: T is for T cell and M is for memory. J Clin Oncol. 2011 Feb 20;29(6):601-3. doi: 10.1200/JCO.2010.32.9078. Epub 2011 Jan 18. No abstract available.
Results Reference
background
PubMed Identifier
21846824
Citation
Halama N, Michel S, Kloor M, Zoernig I, Benner A, Spille A, Pommerencke T, von Knebel DM, Folprecht G, Luber B, Feyen N, Martens UM, Beckhove P, Gnjatic S, Schirmacher P, Herpel E, Weitz J, Grabe N, Jaeger D. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res. 2011 Sep 1;71(17):5670-7. doi: 10.1158/0008-5472.CAN-11-0268. Epub 2011 Aug 16.
Results Reference
background
PubMed Identifier
19258510
Citation
Camus M, Tosolini M, Mlecnik B, Pages F, Kirilovsky A, Berger A, Costes A, Bindea G, Charoentong P, Bruneval P, Trajanoski Z, Fridman WH, Galon J. Coordination of intratumoral immune reaction and human colorectal cancer recurrence. Cancer Res. 2009 Mar 15;69(6):2685-93. doi: 10.1158/0008-5472.CAN-08-2654. Epub 2009 Mar 3.
Results Reference
background
PubMed Identifier
18573340
Citation
Tesniere A, Apetoh L, Ghiringhelli F, Joza N, Panaretakis T, Kepp O, Schlemmer F, Zitvogel L, Kroemer G. Immunogenic cancer cell death: a key-lock paradigm. Curr Opin Immunol. 2008 Oct;20(5):504-11. doi: 10.1016/j.coi.2008.05.007. Epub 2008 Jun 23.
Results Reference
background
PubMed Identifier
16960692
Citation
Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother. 2007 May;56(5):641-8. doi: 10.1007/s00262-006-0225-8. Epub 2006 Sep 8.
Results Reference
background
PubMed Identifier
11325840
Citation
Machiels JP, Reilly RT, Emens LA, Ercolini AM, Lei RY, Weintraub D, Okoye FI, Jaffee EM. Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res. 2001 May 1;61(9):3689-97.
Results Reference
background
PubMed Identifier
19909745
Citation
Mlecnik B, Tosolini M, Charoentong P, Kirilovsky A, Bindea G, Berger A, Camus M, Gillard M, Bruneval P, Fridman WH, Pages F, Trajanoski Z, Galon J. Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer. Gastroenterology. 2010 Apr;138(4):1429-40. doi: 10.1053/j.gastro.2009.10.057. Epub 2009 Nov 10.
Results Reference
background
PubMed Identifier
18024654
Citation
Branford S. Chronic myeloid leukemia: molecular monitoring in clinical practice. Hematology Am Soc Hematol Educ Program. 2007:376-83. doi: 10.1182/asheducation-2007.1.376.
Results Reference
background
PubMed Identifier
18438408
Citation
Campbell PJ, Stephens PJ, Pleasance ED, O'Meara S, Li H, Santarius T, Stebbings LA, Leroy C, Edkins S, Hardy C, Teague JW, Menzies A, Goodhead I, Turner DJ, Clee CM, Quail MA, Cox A, Brown C, Durbin R, Hurles ME, Edwards PA, Bignell GR, Stratton MR, Futreal PA. Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat Genet. 2008 Jun;40(6):722-9. doi: 10.1038/ng.128. Epub 2008 Apr 27.
Results Reference
background
PubMed Identifier
18670422
Citation
Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, Kinzler KW, Vogelstein B, Diaz LA Jr. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008 Sep;14(9):985-90. doi: 10.1038/nm.1789. Epub 2007 Jul 31.
Results Reference
background
PubMed Identifier
19276259
Citation
Yung TK, Chan KC, Mok TS, Tong J, To KF, Lo YM. Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients. Clin Cancer Res. 2009 Mar 15;15(6):2076-84. doi: 10.1158/1078-0432.CCR-08-2622. Epub 2009 Mar 10.
Results Reference
background
PubMed Identifier
20371490
Citation
Leary RJ, Kinde I, Diehl F, Schmidt K, Clouser C, Duncan C, Antipova A, Lee C, McKernan K, De La Vega FM, Kinzler KW, Vogelstein B, Diaz LA Jr, Velculescu VE. Development of personalized tumor biomarkers using massively parallel sequencing. Sci Transl Med. 2010 Feb 24;2(20):20ra14. doi: 10.1126/scitranslmed.3000702.
Results Reference
background
PubMed Identifier
20725990
Citation
McBride DJ, Orpana AK, Sotiriou C, Joensuu H, Stephens PJ, Mudie LJ, Hamalainen E, Stebbings LA, Andersson LC, Flanagan AM, Durbecq V, Ignatiadis M, Kallioniemi O, Heckman CA, Alitalo K, Edgren H, Futreal PA, Stratton MR, Campbell PJ. Use of cancer-specific genomic rearrangements to quantify disease burden in plasma from patients with solid tumors. Genes Chromosomes Cancer. 2010 Nov;49(11):1062-9. doi: 10.1002/gcc.20815.
Results Reference
background

Learn more about this trial

Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Bevacizumab With FOLFOX or FOLFIRI.

We'll reach out to this number within 24 hrs