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Colorectal CancerPhase 2NCT00043004

Chemotherapy and Bevacizumab With or Without Radiofrequency Ablation in Treating Unresectable Liver Metastases in Patients With Colorectal Cancer

A Phase 2 study testing bevacizumab, FOLFOX regimen and fluorouracil in people with Colorectal Cancer and Metastatic Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 43 sites in 10 countries.

Terminated

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

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread by blocking blood flow. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Colorectal Cancer, Metastatic Cancer
What is being tested?
bevacizumab, FOLFOX regimen and fluorouracil
Type of treatment
Surgery or procedure
How many people
119 participants
Where
43 sitesin 10 countries
Study dates
May 2002to Jun 2007
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Unresectable liver metastases secondary to colorectal adenocarcinoma, including:
  • Metastases that cannot be radically resected due to size, location, or number of deposits
  • Metastases invading right and left branches of hepatic artery or portal vein
  • Metastases extended to the 3 main hepatic veins
  • No detectable extra-hepatic disease
  • Fewer than 10 metastatic deposits on liver
  • Total metastatic involvement of liver no more than 50%
  • Adequate treatment of all metastatic lesions deemed possible either by radiofrequency interstitial ablation (RFA) alone or by a combination of resection of resectable lesions and RFA of the remaining unresectable lesions
  • Maximum diameter of 4 cm for lesions to be treated with RFA
  • No maximum diameter of lesions to be resected as long as negative resection margins are obtainable
  • If synchronous liver metastases, must have undergone prior resection of primary tumor

PATIENT CHARACTERISTICS:

Age

  • 18 to 80

Performance status

  • WHO 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3
  • No bleeding disorder or coagulopathy or need for full-dose anticoagulation

Hepatic

  • Bilirubin less than 3 times upper limit of normal (ULN)
  • Alkaline phosphatase less than 3 times ULN

Renal

  • Creatinine less than 2 times ULN
  • Protein < 0.5 g/24 hr urine collection if proteinuria positive by dipstick

Cardiovascular

  • No uncontrolled congestive heart failure
  • No uncontrolled angina pectoris
  • No uncontrolled hypertension
  • No uncontrolled arrhythmia
  • No myocardial infarction within the past 12 months
  • No cerebrovascular accident or transient ischemic attack within the past 6 months

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No greater than grade 1 peripheral neuropathy
  • No significant neurologic or psychiatric disorder
  • No active infection
  • No contraindication to the use of fluorouracil, leucovorin calcium, oxaliplatin, or bevacizumab
  • No other malignancy within the past 10 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy except for metastatic disease confined to the liver
  • Prior fluorouracil, leucovorin calcium, and oxaliplatin allowed if administered for at least 3 courses (2 weeks each) but no longer than 3 months with at least stabilization of disease achieved
  • Prior adjuvant chemotherapy for primary cancer allowed except for patients who received oxaliplatin and have been diagnosed with metastatic disease within 12 months after completion of adjuvant treatment

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • More than 28 days since major surgery or open biopsy past 28 days
  • More than 28 days since significant traumatic injury

Other

  • No other concurrent investigational treatment
  • No other concurrent anticancer therapy

Trial locations and contacts

43 sites in 10 countries.

43 sites in 10 countries

United Kingdom12 sites

  • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

    Birmingham, England, B15 2TH

  • Bristol Haematology and Oncology Centre

    Bristol, England, BS2 8ED

  • Velindre Cancer Center at Velindre Hospital

    Cardiff, Wales, CF14 2TL

  • Leicester General Hospital

    Leicester, England, LE5 4PW

  • Royal Liverpool University Hospital

    Liverpool, England, L69 3GA

  • Cancer Research UK and University College London Cancer Trials Centre

    London, England, NW1 2ND

  • University College of London Hospitals

    London, England, WIT 3AA

  • Manchester Royal Infirmary

    Manchester, England, M13 9WL

  • Clatterbridge Centre for Oncology NHS Trust

    Merseyside, England, CH63 4JY

  • Churchill Hospital

    Oxford, England, OX3 7LJ

  • Glan Clywd District General Hospital

    Rhyl, Denbighshire, Wales, LL 18 5UJ

  • Royal South Hants Hospital

    Southampton, England, SO14 0YG

Other trials in United Kingdom

Netherlands10 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, 5211 NL

  • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

    Amsterdam, 1066 CX

  • Amphia Ziekenhuis - locatie Langendijk

    Breda, 4800 RL

  • Medisch Spectrum Twente

    Enschede, 7500 KA

  • Atrium Medical Centre - Heerlen

    Heerlen, 6401 CX

  • Medisch Centrum Leeuwarden - Zuid

    Leeuwarden, 8934 AD

  • Academisch Ziekenhuis Maastricht

    Maastricht, 6202 AZ

  • Universitair Medisch Centrum St. Radboud - Nijmegen

    Nijmegen, NL-6500 HB

  • University Medical Center Utrecht

    Utrecht, 3584 CX

  • Maxima Medisch Centrum - Veldhoven

    Veldhoven, 5500 MB

Other trials in Netherlands

Belgium5 sites

  • Ziekenhuis Netwerk Antwerpen Middelheim

    Antwerp, 2020

  • Institut Jules Bordet

    Brussels, 1000

  • Universitair Ziekenhuis Antwerpen

    Edegem, B-2650

  • Universitair Ziekenhuis Gent

    Ghent, B-9000

  • Clinique Universitaire De Mont-Godinne

    Mont-Godinne Yvoir, 5530

Other trials in Belgium

Germany5 sites

  • Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch

    Berlin, D-13122

  • Kliniken Essen - Mitte

    Essen, D-45136

  • Klinikum der J.W. Goethe Universitaet

    Frankfurt, D-60590

  • Staedtische Kliniken Frankfurt am Main - Hoechst

    Frankfurt, D-65929

  • Klinikum der Universitaet Regensburg

    Regensburg, D-93053

Other trials in Germany

France4 sites

  • Centre Hospitalier Regional et Universitaire d'Angers

    Angers, 49033

  • Centre Hospitalier Universitaire Ambroise Pare - Boulogne

    Boulogne-Billancourt, F-92104

  • Hopital Universitaire Hautepierre

    Strasbourg, 67098

  • Centre Alexis Vautrin

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Sweden3 sites

  • Sahlgrenska University Hospital at Gothenburg University

    Gothenburg (Goteborg), S-413 45

  • Karolinska University Hospital - Huddinge

    Stockholm, S - 141 86

  • Uppsala University Hospital

    Uppsala, SE 75185

Other trials in Sweden

Austria1 site

  • Allgemeines Krankenhaus - Universitatskliniken

    Vienna, A-1090

Other trials in Austria

Egypt1 site

  • National Cancer Institute - Cairo

    Cairo

Other trials in Egypt

Hungary1 site

  • National Institute of Oncology

    Budapest, 1122

Other trials in Hungary

Italy1 site

  • Azienda Ospedaliera S. Camillo-Forlanini

    Rome, 00152

Other trials in Italy

About this study

Official title: CLOCC Trial (Chemotherapy + Local Ablation Versus Chemotherapy) Randomized Phase II Study Of Local Treatment Of Liver Metastases By Radiofrequency Combined With Chemotherapy Versus Chemotherapy Alone In Patients With Unresectable Colorectal Liver Metastases

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread by blocking blood flow. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiofrequency ablation uses high-frequency electric current to kill tumor cells. It is not yet known if chemotherapy is more effective with or without radiofrequency ablation in treating liver metastases.

PURPOSE: This randomized phase II trial is studying combination chemotherapy, bevacizumab, and radiofrequency ablation to see how well they work compared to combination chemotherapy and bevacizumab alone in treating unresectable liver metastases in patients with colorectal cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Compare the 30-month overall survival rate of patients with unresectable liver metastases secondary to colorectal adenocarcinoma treated with chemotherapy and bevacizumab with or without radiofrequency interstitial ablation.

Secondary

  • Compare overall survival of patients treated with these regimens.
  • Compare quality of life of patients treated with these regimens.
  • Determine the health economics associated with this study.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to treatment center, prior adjuvant chemotherapy for primary cancer (yes vs no), prior chemotherapy for liver metastases (yes vs no), and route of randomization (before surgery vs during surgery). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Within 4 weeks of randomization, patients undergo radiofrequency interstitial ablation (RFA) with or without additional resection of resectable lesions. Within 8 weeks after RFA, patients receive chemotherapy and bevacizumab.
  • Arm II: Within 4 weeks of randomization, patients receive chemotherapy and bevacizumab.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients in both arms receive one of the following chemotherapy and bevacizumab regimens to be determined by participating center:

  • Regimen A: Patients receive oxaliplatin IV over 2 hours on day 1 of weeks 1, 3, and 5 and leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 24 hours on day 1 of weeks 1-6 and bevacizumab IV over 30-90 minutes on days 1 or 2, 15 or 16, and 29 or 30. Treatment repeats every 7 weeks for 4 courses.
  • Regimen B: Patients receive oxaliplatin IV and leucovorin calcium IV over 2 hours on day 1 followed by fluorouracil IV continuously over 46 hours and bevacizumab IV over 30-90 minutes on day 1 or 3. Treatment repeats every 15 days for 12 courses.
  • Regimen C: Patients receive oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 22 hours on days 1 and 2 and bevacizumab IV over 30-90 minutes on day 1 or 3. Treatment repeats every 15 days for 12 courses.

Quality of life is assessed at baseline, within 1 week after completion of RFA (arm I only), within 1 week before start of chemotherapy (arm I only), at weeks 6, 12, 18, and 24 during chemotherapy, every 3 months for 2 years after treatment, and then every 6 months thereafter.

After completion of study treatment, patients are followed every 3 months for 2½ years and then every 6 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 152 patients (71 per treatment arm) will be accrued for this study within 3 years.

Keywords
liver metastases, stage IV colon cancer, stage IV rectal cancer
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis, Colonic Neoplasms, Rectal Neoplasms

What participants receive

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

What is being measured

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

  1. Survival rate as measured by Kaplan Meier method at 30 months

Secondary outcomes (5)

  1. Overall survival as measured by Logrank every 3 months for 30 months then every 6 months thereafter

  2. Progression-free survival as measured by Logrank every 3 months for 30 months then every 6 months thereafter

  3. Toxicity as measured by CTC version 2.0 every 3 months for 30 months then every 6 months thereafter

  4. Quality of life as measured by Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 at baseline, weeks 6, 12, 18, and 24, every 3 months for years 1-2 after start of treatment, then every 6 months thereafter

  5. Response to treatment (arm II) as measured by RECIST criteria from start of treatment until disease progression

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startMay 2002
  3. Primary completionJun 2007

Why it stopped: low accrual

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
Masking
None (open label)
Enrolment
119 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00043004
Sponsor's protocol ID
EORTC-40004
Other IDs
EORTC-40004, ALM-CAO-EORTC-40004, NCRI-EORTC-40004
Status last verified
Sep 2012
First submitted
5 Aug 2002
Last updated
24 Sep 2012
Results posted
No

Publications

  • Ruers T, van Coevorden F, Pierie J, et al.: Radiofrequency ablation (RFA) combined with chemotherapy for unresectable colorectal liver metastases (CRC LM): interim results of a randomised phase II study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC). [Abstract] J Clin Oncol 26 (Suppl 15): A-9535, 2008.

  • Ruers T, Punt C, Van Coevorden F, Pierie JPEN, Borel-Rinkes I, Ledermann JA, Poston G, Bechstein W, Lentz MA, Mauer M, Van Cutsem E, Lutz MP, Nordlinger B; EORTC Gastro-Intestinal Tract Cancer Group; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO) and the National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG). Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol. 2012 Oct;23(10):2619-2626. doi: 10.1093/annonc/mds053. Epub 2012 Mar 19.

    PubMed 22431703

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab, FOLFOX regimen and fluorouracil in people with Colorectal Cancer and Metastatic Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 43 sites in 10 countries.

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

Who may be eligible to take part?

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 24 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United Kingdom, Netherlands, Belgium, Germany, France and 5 more countries. 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: low accrual). 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?

Survival rate as measured by Kaplan Meier method at 30 months. 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 NCT00043004, which also lists 2 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 24 Sep 2012.

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