AzTrials
AzTrials

Metastatic Colorectal CancerPhase 2NCT01858662

Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Treatment Combining Cetuximab With FOLFOX or FOLFIRI in RAS and B-RAF WT Tumors

A Phase 2 study testing Metastases Resection ( multiple steep surgery possible), 5-Fluorouracile and leucovorin L in people with Metastatic Colorectal Cancer, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 7 sites in Belgium.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

To analyze the pathological tumor response on resected colorectal cancer metastases after preoperative treatment with cetuximab combined with FOLFOX or FOLFIRI regimen in a prospective cohort (RAS and B-RAF WT tumors) and to correlate this response with patient's outcome. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Metastases Resection ( multiple steep surgery possible), 5-Fluorouracile and leucovorin L
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
7 sitesBelgium
Study dates
Jan 2014to Nov 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female or male patients with at least 18 years at the time the informed consent is signed
  • ECOG performance status 0 or 1
  • Histological or cytological confirmed diagnostic of adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Wild-type RAS and B-RAF tumor status.
  • Patients with potentially resectable metastatic disease at diagnosis and for whom a chemotherapy first in a curative intent is recommended . Resectability could be planed 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.
  • Partial and minor resection of metastatic disease is allowed within 3 months before inclusion if patient has never received chemotherapy for mCRC.
  • Extra hepatic metastatic location is limited to 1 site.
Show all 17Show fewer
  • 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.
  • Adequate haematological, renal and hepatic function as follows:
  • Haematological:
  • haemoglobin >9g/dl Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L
  • Renal:
  • Creatinine< 1.5 x ULN (Upper Limit of Normal)
  • Hepatic:
  • Bilirubin < or equal 1.5 X ULN AST (Aspartate Aminotransferase),and ALT (Alanine Aminotransferase)< or equal 5 x ULN, Phos Alc< or equal 5 x ULN
  • Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception.
  • Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception.
  • Life expectancy of at least 3 months without any active treatment.

Who cannot join

  • 1.Definitively non resectable mCRC at diagnosis
  • 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 cetuximab, panitumumab (or other anti-EGFR (epidermal growth factor receptor)therapy).
  • 4.Previous radiotherapy delivered to the upper abdomen.
  • 5 Non mesurable disease( RECIST 1.1 criteria)
  • 6.Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiologic assessment.
Show all 13Show fewer
  • 7.Prior major liver resection: remnant liver < 50% of the initial liver volume.
  • 8.Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.
  • 9.Concurrent central nervous systems metastases
  • 10.Peripheric neuropathy ≥ grade 2.
  • 11.Interstitial lung disease
  • 12.Pregnant or breast feeding.
  • 13.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.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Belgium7 sites

  • clinique Saint Luc

    Bouge, 5004

  • Cliniques universitaires Saint-Luc - UCL

    Brussels, Brussels Capital, 1200

  • Grand Hôpital de Charleroi

    Charleroi, Hainaut, 6000

  • Centre Hospitalier Jolimont Lobbes

    La Louvière, 7100

  • CHU liège (Sart Timan)

    Liège, 4000

  • Clinique Saint Pierre Ottignies

    Ottignies, 1340

  • CHU-UCL Dinant-Godinne

    Yvoir, 5530

Other trials in Belgium

About this study

Official title: Randomised Phase 2 Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Treatment Combining Cetuximab With FOLFOX or FOLFIRI in RAS and B-RAF WT Tumors

To analyze the pathological tumor response on resected colorectal cancer metastases after preoperative treatment with cetuximab combined with FOLFOX or FOLFIRI regimen in a prospective cohort (RAS and B-RAF WT tumors) and to correlate this response with patient's outcome.

Read the detailed description

This is a phase II , openlabel, randomized study in patients with confirmed diagnosis of potentially or borderline resectable metastatic colorectal adenocarcinoma (RAS and B-RAF WT tumors ), who have not received prior chemotherapy for their metastatic disease.

The study is designed to compare pathological responses observed after pre-operative chemotherapy cetuximab with FOLFOX or FOLFIRI.

Being tested
Metastases Resection ( multiple steep surgery possible), 5-Fluorouracile, leucovorin L, Oxaliplatin, Irinotecan
Keywords
metastatic colorectal cancer, Liver, cetuximab, Pathological response
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Metastases Resection ( multiple steep surgery possible)Procedure or surgery

    Metastases resection will be process by surgery, after a randomized chemotherapy (FOLFOX or FOLFIRI) + Target therapy (Cetuximab). The surgery will allow to compare the pathological response on the resected metastases by the chemotherapy + target therapy type.

  • 5-FluorouracileDrug

    Also called 5FU

    5-FU bolus 400 mg/m2, IV bolus every 2 weeks 5-FU continuous infusion 2400 mg/m2, 46-hour cont. IV infusion every 2 weeks

  • leucovorin LDrug

    Also called elvorine, isovorin

    Leucovorin L (levoleucovorin) 200 mg/m2 (or folinic acid 400 mg/m²) in 250 ml glucose 5%, 2-hour IV infusion

  • OxaliplatinDrug

    Also called Eloxatin

    Oxaliplatin 85 mg/m² in 150 ml NaCl 0.9%, 2-hour IV infusion every 2 weeks

  • IrinotecanDrug

    Also called Campto, Irinosin

    Irinotecan 180 mg/m² in 150 ml NaCl 0.9%, 1.30-hour IV infusion every 2 weeks

  • CetuximabDrug

    Also called erbitux

    Cetuximab 400 mg/m² in 100 ml NaCl 0.9% 2-hour IV infusion for 1rst cycle and after the 1rst cycle 250 mg/m² in 100 ml NaCl 0.9% 1-hour IV infusion

Study groups in NCT01858662
Study groupRoleWhat they receive
oxaliplatin +leucovorin L+5FU+ cetuximabActive comparatoroxaliplatin +leucovorinL+5-Fluorouracile +cetuximab+'Metastases Resection ( multiple steep surgery possible)
Receives: Procedure: Metastases Resection ( multiple steep surgery possible); Drug: 5-Fluorouracile; Drug: leucovorin L; Drug: Oxaliplatin; Drug: Cetuximab
Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximabActive comparatorIrinotecan+ + leucovorinL +5-Fluorouracile + cetuximab +'Metastases Resection ( multiple steep surgery possible)
Receives: Procedure: Metastases Resection ( multiple steep surgery possible); Drug: 5-Fluorouracile; Drug: leucovorin L; Drug: Irinotecan; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major Pathological Response Rate

    Major pathological response rate (MPRR) is defined as the proportion of patients presenting a major pathological response. Pathologic response will be evaluated according the Rubbia-Brandt Tumor Regression Grade classification .For patients with multiple colorectal metastases the global pathological response will be categorized based on the mean TRG of all metastases.: a major response is defined as a mean TRG < 3, a partial response is defined for patient presenting a mean TRG ≥3 and <4, and a no response for patient with a mean TRG ≥4.

    Measured: Average 3 months (after resection of metastases)

Secondary outcomes (7)

  1. progression free survival

    -Progression Free Survival (PFS) is defined as the time from randomization to the time of first event (relapse of the original mCRC, development of a new colorectal cancer or death due to any cause). Patients without any such event at the time of data analysis will be censored at the last date they were known to be event-free. PFS analysis will be based on tumour assessments and survival follow-up assessments.

    Measured: at 6 months and at 12 months after randomization

  2. Overall survival

    The overall survival will be analyzed at the end of study (3 year of recruitment and one year of follow-up).

    Measured: At the end of the study

  3. Clinical response rate

    Clinical response rate at time of surgery: Clinical tumour response will be measured according to the RECIST 1.1 criteria

    Measured: at time of surgery -

  4. Metabolic response rate

    Metabolic response rate at time of surgery (in selected centres only, optional): Metabolic tumour response will be measured according to the EORTC criteria . PET-Scan evaluation remains optional to selected centres only.

    Measured: At time of surgery - average 3 months

  5. post operative complications

    . Severe pre- or postoperative complications within 30 days of surgery:

    • surgery-associated bleeding requiring replacement with > 4 units of erythrocyte concentrates,
    • wound infection,
    • intra-abdominal infection,
    • severe sepsis (American College of Chest physicians/Society of Critical Care Medicine, 1992),
    • impaired wound healing,
    • subphrenic or perihepatic abscess requiring drainage during hospital stay or within 30 days after the operation,
    • re-laparotomy connected with the resection,
    • a biliary fistula for more than 10 days with a discharge of > 100 mL/day,
    • transient liver failure (bilirubin > 10 mg/dL lasting > 3 days),
    • renal failure requiring dialysis,
    • respiratory failure with renewed necessary mechanical ventilation, venous thromboembolism,
    • cardiac failure,
    • death of the patient as a result of the operation.

    Measured: one month after surgery

  6. Curative resection rate

    Curative resection rate (R0 resection) is defined by the surgical clearance (+/- radiofrequency ablation) of all detectable hepatic lesions with tumor-free margins at histo-pathological evaluation.

    Measured: At time of surgery

  7. Chemotherapy-associated hepatotoxicity:

    Systemic neo-adjuvant chemotherapy in mCRC frequently causes morphological lesions involving hepatic microvasculature . Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non tumoral liver, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplatin.

    Measured: at time of surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2013 (estimated)
  2. Study startJan 2014
  3. Primary completionNov 2015
  4. Study completionNov 2015

Why it stopped: due to poor recrutment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01858662
Sponsor's protocol ID
CET-ONCO2012
Other IDs
2012-005249-19
Status last verified
Apr 2016
First submitted
7 May 2013
Last updated
15 Apr 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 19474385

  • 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.

    PubMed 9161393

  • 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.

    PubMed 8608500

  • 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.

    PubMed 18156932

  • 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.

    PubMed 18358928

  • 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.

    PubMed 15175435

  • 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.

    PubMed 18421054

  • 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.

    PubMed 21502544

  • 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.

    PubMed 22446022

  • 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.

    PubMed 20921465

  • 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.

    PubMed 17532622

  • 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.

    PubMed 17449351

  • 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.

    PubMed 15175436

  • 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.

    PubMed 18398148

  • 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.

    PubMed 20177795

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metastases Resection ( multiple steep surgery possible), 5-Fluorouracile and leucovorin L in people with Metastatic Colorectal Cancer, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 7 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: due to poor recrutment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major Pathological Response Rate (time frame: Average 3 months (after resection of metastases)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01858662, which also lists 54 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in