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

This study has been terminated.
(low accrual)
Sponsor:
Collaborators:
Arbeitsgruppe Lebermetastasen und Tumoren
Institute of Cancer Research, United Kingdom
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00043004
First received: August 5, 2002
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Metastatic Cancer
Biological: bevacizumab
Drug: FOLFOX regimen
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Procedure: conventional surgery
Procedure: radiofrequency ablation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Survival rate as measured by Kaplan Meier method at 30 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival as measured by Logrank every 3 months for 30 months then every 6 months thereafter [ Designated as safety issue: No ]
  • Progression-free survival as measured by Logrank every 3 months for 30 months then every 6 months thereafter [ Designated as safety issue: No ]
  • Toxicity as measured by CTC version 2.0 every 3 months for 30 months then every 6 months thereafter [ Designated as safety issue: Yes ]
  • 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 [ Designated as safety issue: No ]
  • Response to treatment (arm II) as measured by RECIST criteria from start of treatment until disease progression [ Designated as safety issue: No ]

Enrollment: 119
Study Start Date: May 2002
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00043004

  Show 43 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Arbeitsgruppe Lebermetastasen und Tumoren
Institute of Cancer Research, United Kingdom
Investigators
Study Chair: Theo Ruers, MD Universitair Medisch Centrum St. Radboud - Nijmegen
Study Chair: Wolf O. Bechstein, MD Arbeitsgruppe Lebermetastasen und Tumoren
Study Chair: Jonathan A. Ledermann, MD Cancer Research UK
  More Information

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00043004     History of Changes
Other Study ID Numbers: EORTC-40004, EORTC-40004, ALM-CAO-EORTC-40004, NCRI-EORTC-40004
Study First Received: August 5, 2002
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
liver metastases
stage IV colon cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases
Fluorouracil
Oxaliplatin
Bevacizumab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 01, 2014