Study Comparing Radio Frequency Ablation Plus Chemotherapy and Chemotherapy Alone in Patients With Secondary Liver Metastases (Prometheus)

March 2, 2017 updated by: Boston Scientific Corporation

A Prospective, Randomized, Active-Control, Multi-Center Study Assessing Overall Survival Using Chemotherapy With or Without Impedance-Based Radiofrequency Ablation for Subjects With Colorectal Cancer and Incurable Metastatic Liver Disease, Failing at Least First-Line Chemotherapy

The purpose of this study is to determine whether patients treated with Radiofrequency Ablation (RFA) in conjunction with chemotherapy have a better overall survival rate than patients treated with chemotherapy alone.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The American Cancer Society has estimated that colorectal cancer is the second leading cause of cancer related deaths, with 106,370 new cases diagnosed in 2004. Due to the unique nature of the hepatic circulatory system, with preferential portal venous drainage of the gastrointestinal tract, the liver is the most common site for metastatic tumor growth from a colorectal carcinoma. It is estimated that approximately 20% of patients diagnosed with colorectal cancer will present with liver involvement at the time of diagnosis, and 50% of patients will manifest metastatic involvement of the liver following resection of the primary colorectal cancer. Over one half of patients who die of colorectal cancer have liver metastases at autopsy.

The current "gold standard" in the treatment of isolated metastatic liver disease is curative hepatic resection. Only within the last 20 years has surgical resection become a viable option, as in the past it was considered unjustified due to high morbidity and mortality rates. The primary drawback to hepatic resection is the sheer number of patients for whom it is contraindicated. Only 10-20% of patients liver metastases are candidates for surgical resection, owing to factors such as tumor locations, size, extent of disease, and other medical co-morbidities.

Historically, in cases where hepatic resection was contraindicated, systemic chemotherapy was the only alternative treatment. In the last several years an increasing number of hepatic directed therapies have become available such as hepatic artery ligation, radiation, hepatic artery infusion of chemotherapy, chemoembolization, and mechanical ablation of the tumor(s).

One mechanical method of ablation involves the use of radiofrequency thermal technology, also called radiofrequency ablation (RFA). The RFA procedure involves inserting an RF electrode into the center of a hepatic tumor mass under ultrasonic or CT guidance. Radiofrequency energy is then applied through the electrode, causing a thermal injury to the surrounding tumor tissue. Currently there are two basic designs for monitoring inter-procedural progress during RFA; temperature monitoring of set points within the target tissue with thermocouples, or assessing the system-wide impedance of tissue adjacent to the deployed electrode tines. Radiofrequency ablation systems are comprised of three components: a radiofrequency generator, an active electrode, and dispersive electrodes.

To date no prospective multi-center trials have been completed which would conclusively demonstrate whether RFA is an effective adjunct to systemic chemotherapy with respect to advantages in median overall survival compared with chemotherapy alone. The primary objective of this trial is to determine overall survival for subjects with colorectal cancer and incurable metastatic liver disease who fail at least first line chemotherapy and are treated with radiofrequency ablation plus additional chemotherapy, compared to subjects receiving additional chemotherapy only.

Study Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • New York University
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • The Cleveland Clinic Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

All subjects must meet the following criteria:

  • Subject must have incurable metastatic colorectal cancer with metastatic disease to the liver
  • Subject must have extrahepatic metastatic disease, as confirmed by radiographic evidence or surgical/other documentation that cannot be treated by surgery or image guided therapy to an endpoint of no evidence of residual disease by imaging criteria
  • Subject has received and, in the opinion of the treating physician, progressed through at least one prior chemotherapy regimen for metastatic disease, or has developed recurrent disease on or within 6 months of completing adjuvant therapy
  • At least 50% of the total tumor burden is in the liver, as determined by the treating investigator, and prior to any study specified intervention (resection or ablation).
  • Subject must have no more than 10 hepatic tumors remaining after surgical resection, with no tumor exhibiting a unidimensional size greater than 5cm
  • Subject is medically eligible to receive RFA, as determined by the treating investigator
  • Subject is naïve to, and medically eligible (as defined by the treating investigator) to receive, at least one of the following:
  • an oxaliplatin containing regimen
  • an irinotecan containing regimen
  • an anti-EGFR monoclonal antibody-containing regimen (subject must be naïve to both cetuximab and panitumumab)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
  • Age > 18 years
  • Subject life expectancy > 3 months
  • International Normalized Ratio (INR) < 2.0
  • Platelets > 100 x103/mm3
  • Total Bilirubin <1.5mg/dl
  • Creatinine level < 2.0 mg/dl
  • Must sign an Informed Consent form

Exclusion Criteria:

All subjects who meet any of the following criteria will not be enrolled into the study:

  • Subjects's extrahepatic disease is amenable to curative surgical or image guided therapy
  • Subject has known brain metastases
  • Uncorrectable coagulopathy
  • Subject is pregnant, nursing, or wishes to become pregnant during the study
  • Other serious medical condition(s) (e.g. uncontrolled infection, uncontrolled cardiac disease) that, in the opinion of the treating investigator, would preclude study treatment or impact survival.
  • Current or planned treatment with any experimental chemotherapy or biological agents

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Radiofrequency ablation in conjunction with chemotherapy
Device: Radiofrequency Ablation (RFA)
The RF3000 radiofrequency generator has the capacity to deliver 200 watts of alternating current to the needle electrode for the coagulation necrosis of soft tissue.
Other Names:
  • RF3000 Radiofrequency (RF) Generators
  • LeVeen Electrode
  • Co-Access Electrode
  • Soloist Electrode
  • SuperSlim Electrode
Active Comparator: B
Standard of care chemotherapy regimen
Drug: Chemotherapy
Standard of care chemotherapy regimen
Other Names:
  • Oxaliplatin containing chemotherapy regimen
  • Irinotecan containing chemotherapy regimen
  • An anti-EGFR monoclonal antibody-containing regimen
  • Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To evaluate Overall Survival in subjects receiving chemotherapy + RFA compared to chemotherapy alone.
Time Frame: Study duration
Study duration

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate any unanticipated adverse device effects.
Time Frame: Two years
Two years
To determine if there are differences in the incidence or severity of adverse events in the RFA + chemotherapy arm compared to the chemotherapy only arm.
Time Frame: Study duration
Study duration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston Scientific Corporation

Investigators

  • Study Director: William Jacqmein, Boston Scientific Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Study Completion (Anticipated)

December 1, 2010

Study Registration Dates

First Submitted

July 31, 2007

First Submitted That Met QC Criteria

August 1, 2007

First Posted (Estimate)

August 2, 2007

Study Record Updates

Last Update Posted (Actual)

March 3, 2017

Last Update Submitted That Met QC Criteria

March 2, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONC-PM-032006

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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