Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Colonic Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Herbal and Botanical

Irinotecan

Cetuximab

Liver Extracts

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Cola

SIR-Spheres with Cetuximab + Irinotecan Therapy

SIR-Spheres, resin microspheres containing pure Beta emitter Yttrium-90, given through femoral catheter over 10 minutes.

SIR-spheres Agent Administration

400 mg/m2 by vein over 2 hours once a week.

Cetuximab infusions will be continued weekly at a dose of 250 mg/m2 unless toxicity necessitates interruptions.

350 mg/m2 (or 300 mg/m2 in patients who are greater or equal to 70 years of age, or have an ECOG PS of 2 or have had prior pelvic and/or abdominal irradiation), by vein over 90 minutes, every three weeks.

Ravi Murthy, MD

The goal of this clinical research study is to find out what effects radioactive particles, SIR-spheres, have when injected into the liver, followed by systemic chemotherapy with a combination of cetuximab and irinotecan compared to those who have systemic therapy alone, in patients with colon cancer that has metastasized to the liver. The safety of this treatment and how well it controls the disease will also be studied.

Yttrium microspheres are designed to treat cancer that has metastasized to the liver by giving radiation directly to the tumor. SIR-spheres are designed to deliver radiation directly to the tumor. This radiation kills the tumor cells.

Cetuximab is a drug that blocks epidermal growth factor receptor (EGFR). EGFR may be involved in certain types of cancer, including non small-cell lung cancer (NSCLC). When EGFR is stimulated, a series of chemical reactions start that result in a tumor being "told" to grow. Cetuximab tries to stop these reactions by blocking EGFR. This may stop tumors from growing.

Irinotecan is designed to block cell growth by blocking an enzyme that repairs DNA, the building blocks of cells.

If you agree to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1of 2 groups. Participants in one group will receive the SIR-spheres with Cetuximab and Irinotecan therapy. Participants in the other group will just have the Cetuximab and Irinotecan therapy without the SIR-spheres. There is an equal chance of being assigned to either group.

If you are found to be eligible to take part in this study, you will have a blood vessel study (given with x-ray dye) performed. This will help researchers look at the arteries leading to your liver and the surrounding areas. You will receive Versed and Fentanyl, sedative drugs to put you to sleep, intravenously (IV--through a needle in a vein) in your arm. A catheter will be placed through your groin artery into the artery leading to your liver. A catheter is a sterile flexible tube that will be placed into a large artery while you are under local anesthesia and IV sedation. Your physician will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure. X-ray dye will be injected through the catheter.

If randomly selected to receive the SIR-Spheres with Cetuximab and Irinotecan therapy, a small amount of radioactive albumin injection (a part of a scan test used to measure the supply of blood through the lungs) will be given to your liver. Images will then be taken to learn if too much of this material (radioactive particles) shows up in your lungs and if your liver anatomy is normal. If everything appears normal, the yttrium microspheres will be given slowly through the catheter in 1 dose. If your liver anatomy is abnormal, the yttrium microspheres will be given slowly through the catheter in 2 doses. After you are given the yttrium microspheres, the catheter will be removed, and pressure will be applied to your groin to stop any bleeding. You will then be monitored for 6 hours to check on your well being. You will be given pain medication, if needed (the same sedative drugs used before).

You will be given standard doses of Zantac (ranitidine) to help to protect the stomach during treatment. Chemotherapy with cetuximab and irinotecan will be given on an outpatient basis. A catheter (PICC line, port-a-cath) may be inserted through a vein in your arm or chest to ensure that the chemotherapy is given without interruption. Irinotecan will be given by IV over 90 minutes, once every 3 weeks. Cetuximab will be given once a week. On Day 1 of treatment, you will be given a test dose of cetuximab, to check for any allergic reactions. After that, cetuximab will be given by IV over 2 hours. Before every dose of cetuximab, you will be given a dose of diphenhydramine by IV, to keep from having any allergic reactions. You will also receive medication to prevent nausea, vomiting, or an allergic reaction.

You will have a single-photon emission computerized tomography (SPECT) scan within 1 week after your treatment. A SPECT scan lets your doctor study the function of your internal organs. You will have blood (about 2 tablespoons) drawn every week for the first 2 months and then once a month on an outpatient basis. This is so researchers can check the function of your kidneys and liver. You will also have a routine physical exam and a computerized tomography (CT) scan performed once a month to check the growth of your tumor. Researchers will check to see if your tumor is responding to the study treatment by looking at the imaging on CT scans every 8 weeks.

You may be taken off this study if your disease gets worse, if you experience intolerable side effects, or if there is not enough of the study drug supply to continue treating your disease.

You will be followed-up by telephone for as long as you have cancer.

This is an investigational study. Yttrium microspheres are FDA approved for hepatic arterial therapy and treatment of liver metastases. Sir-Sphere therapy has been approved for treating colorectal cancer with liver metastases. The combination of cetuximab and irinotecan is FDA approved for metastatic colorectal cancer. Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.

Yttrium Microspheres With Cetuximab Plus Irinotecan for Patients With Advanced Colorectal Cancer Mets to Liver

Phase II Randomized Study of SIR-Spheres, Yttrium Microspheres With Cetuximab Plus Irinotecan for Patients With Advanced Colorectal Cancer Metastases to the Liver

Sirtex Medical

M.D. Anderson Cancer Center

Carcinoma, Hepatocellular

Liver Neoplasms

Carcinoma

Liver Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Sorafenib

Protein Kinase Inhibitors

Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).

Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).

radiofrequency ablation

Andrea Bullock, MD, MPH

The purpose of this research study is to determine if sorafenib improves the effectiveness of a procedure called radiofrequency ablation (RFA) for the treatment of hepatocellular cancer (HCC). Radiofrequency ablation has been used to treat many types of tumors, including hepatocellular cancers. During RFA a needle is inserted into the tumor tissue and heat is used to kill the tumor cells. Sorafenib has been approved by the FDA for the treatment of hepatocellular cancer that cannot be treated with surgery. Pre-clinical data suggests that sorafenib may improve the efficacy of RFA.

Hepatocellular cancer (HCC) has a poor prognosis with increasing mortality in the United States. Because HCC generally develops in patients with underlying liver disease, resection is often not possible. Liver transplant improves survival for HCC patients but given the national organ donor shortage often patients have to wait a considerable time for transplant. Liver-directed therapies such as radiofrequency ablation (RFA) remain important tools to control tumor growth and to potentially "bridge" patients to liver transplant. However, liver-directed therapies for HCC tumors greater than 3cm in size are suboptimal, leaving a critical unmet need.

Antiangiogenic systemic agents, such as oral sorafenib, reduce tumor blood flow and have been shown to improve RFA efficacy in animal and in computer models.

Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

Randomized, Double-Blind, Placebo-Controlled, Phase II Trial Of Short Course Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized (3.5 to 7cm) Hepatocellular Cancer

The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

Feasibility rate is defined as the percentage of participants completing radiofrequency ablation following 9 days of sorafenib or placebo therapy.

AEs were assessed based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v3.0). The number of Grade 1-4 AEs with treatment attribution possibly, probably or definitely related up to day 9 of study drug treatment were counted for this outcome. Worst grade by patient within AE type was calculated. Participants could have multiple different AE types within a grade.

AEs were assessed based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v3.0). The number of Grade 1-4 AEs with treatment attribution possibly, probably or definitely related on day of RFA treatment were counted for this outcome. Worst grade by patient within AE type was calculated. Participants could have multiple AE types within a grade.

AEs were assessed based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v3.0). The number of Grade 1-4 AEs with treatment attribution possibly, probably or definitely related one month after RFA treatment were counted for this outcome. Worst grade by patient within AE type was calculated. Participants could have multiple AE types within a grade.

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Bayer

Onyx Therapeutics, Inc.

National Cancer Institute (NCI)

Beth Israel Deaconess Medical Center

Principal Investigator

Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. The analysis population is all treated patients (n=1 dropped out before starting treatment.

Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).

Sorafenib

radiofrequency ablation

Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).

radiofrequency ablation

Placebo

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Present Liver Cirrhosis

Present Portal Vein Thrombosis

Tumor Size - Short Axis

Tumor Size - Long Axis

The analysis population is comprised of all enrolled participants.

This study is limited by small sample size.

Andrea Bullock MD, MPH

The analysis population is comprised of all participants who completed treatment ending with day 10 RFA.

Coagulation Zone Diameter-Short Axis

The analysis population is comprised of all participants who completed treatment ending with RFA.

Coagulation Zone Diameter-Long Axis

Assuming the two trial arms were independent, the standard deviation was 0.5cm for both arms and a sample size of 16 evaluable patients (8 per arm), the study had an 84% power at a 5% (two-sided) significance level to detect 0.8cm difference in ablation zone size. In order to allow a 20% drop-out rate, a total of 20 subjects were accrued.

Coagulation Zone Volume

Feasibility Rate

The analysis population is comprised of all treated participants.

Number of Treatment-Related Grade 1-4 Adverse Events (AEs) by Day 9

Number of Treatment-Related Grade 1-4 Adverse Events (AEs) on Day of Radiofrequency Ablation (RFA)

The analysis population is comprised of all treated participants who were evaluable for AEs at day40.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Yttrium Microspheres With Cetuximab Plus Irinotecan for Patients With Advanced Colorectal Cancer Mets to Liver	NCT00766220	Colon Cancer Colorectal Canc...	SIR-spheres Age... Cetuximab Irinotecan	18 Years -	M.D. Anderson Cancer Center
Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer	NCT00813293	Hepatocellular ...	Sorafenib radiofrequency ...	18 Years -	Beth Israel Deaconess Medical Center
Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer	NCT00813293	Hepatocellular ...	Sorafenib radiofrequency ...	18 Years -	Beth Israel Deaconess Medical Center

Spots Global Cancer Trial Database for liver directed therapy