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

• To evaluate Overall Survival in subjects receiving chemotherapy + RFA compared to chemotherapy alone. [ Time Frame: Study duration ]
  

• To evaluate any unanticipated adverse device effects. [ Time Frame: 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 ]
  

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.