Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

NCT ID: NCT01285102

Last Updated: 2021-12-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2013-01-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Chemoembolization kills tumor cells by blocking blood flow to the tumor and keeping chemotherapy drugs near the tumor.

PURPOSE: This phase II trial is studying how well chemoembolization using irinotecan works in treating patients with liver metastases from metastatic colon or rectal cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. To define the response rate of colorectal liver metastases (in the treated lobe) treated with DEBIRI, in refractory mCRC patients.

SECONDARY OBJECTIVES:

I. To evaluate the time to progression in the treated lobe for this patient population.

II. To evaluate the overall survival for this patient population. III. To evaluate patient tolerance and the toxicity profile of treatment with DEBIRI in this patient population.

OUTLINE:

Patients receive irinotecan-eluting beads via hepatic artery embolization every 3 weeks for up to 3 (unilobar disease) or 4 (bi-lobar disease) courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Conditions

Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive irinotecan-eluting beads via hepatic artery embolization every 3 weeks for up to 3 (unilobar disease) or 4 (bi-lobar disease) courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

irinotecan-eluting beads

Intervention Type: COMBINATION_PRODUCT

Patients will be treated with drug-eluting irinotecan beads per protocol at up to 100 mg per dose every 3 weeks. Patients will receive chemoembolization using LC Bead, loaded with irinotecan. The beads size range used in the study will be 100-300µm (nominal) with a dose of up to 100mg irinotecan per treatment. The beads will be mixed with a non-ionic contrast media in the vial immediately prior to use according to the instructions for use. Irinotecan will be loaded onto the beads not more than 2 hours prior to the procedure. The study goal will be to deliver the full dose of 100mg of irinotecan per treatment

hepatic artery embolization

Intervention Type: PROCEDURE

Using a unilateral femoral approach, selective catheterization of the hepatic artery will be performed. Vascular access is obtained via the common femoral artery and a guide-wire advanced under fluoroscopic guidance. A microcatheter is then inserted over the guide-wire. The superior mesenteric artery is selected and an angiogram performed to identify any aberrant arterial anatomy and verify antegrade portal vein flow. The celiac axis is then selected and an angiogram completed. The catheter and guide-wire are used to select the proper hepatic artery and a limited angiogram performed to identify the branches of the hepatic artery. The right or left hepatic artery is selected distal to the cystic artery (if visualized), depending on the location of the lesions to be treated. The LC Bead, loaded with irinotecan will be delivered into the artery.

Interventions

irinotecan-eluting beads

Patients will be treated with drug-eluting irinotecan beads per protocol at up to 100 mg per dose every 3 weeks. Patients will receive chemoembolization using LC Bead, loaded with irinotecan. The beads size range used in the study will be 100-300µm (nominal) with a dose of up to 100mg irinotecan per treatment. The beads will be mixed with a non-ionic contrast media in the vial immediately prior to use according to the instructions for use. Irinotecan will be loaded onto the beads not more than 2 hours prior to the procedure. The study goal will be to deliver the full dose of 100mg of irinotecan per treatment

Intervention Type: COMBINATION_PRODUCT

hepatic artery embolization

Using a unilateral femoral approach, selective catheterization of the hepatic artery will be performed. Vascular access is obtained via the common femoral artery and a guide-wire advanced under fluoroscopic guidance. A microcatheter is then inserted over the guide-wire. The superior mesenteric artery is selected and an angiogram performed to identify any aberrant arterial anatomy and verify antegrade portal vein flow. The celiac axis is then selected and an angiogram completed. The catheter and guide-wire are used to select the proper hepatic artery and a limited angiogram performed to identify the branches of the hepatic artery. The right or left hepatic artery is selected distal to the cystic artery (if visualized), depending on the location of the lesions to be treated. The LC Bead, loaded with irinotecan will be delivered into the artery.

Intervention Type: PROCEDURE

Other Intervention Names

DEBIRI

Eligibility Criteria

Inclusion Criteria

• Patients must have a histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic to the liver and for which standard curative measures do not exist
• Patients must have received prior irinotecan-based treatment for their disease and had documented progression by RECIST criteria; patients must also have received prior fluoropyrimidine and oxaliplatin-based therapy
• Liver disease must not be amenable to potentially curative surgical resection
• Patients must have liver-only or liver-predominant disease to be eligible for this study; hepatic disease must be dominant, but patients are allowed to have extrahepatic disease provided it is not judged likely to be life threatening within 3 months
• Patients must have a patent portal vein as documented by CT, MRI, or ultrasound
• Prior radiation therapy is allowed but must have been completed >= 4 weeks prior to study entry; patients with history of prior radiation to the liver including radio-labeled microspheres cannot take part in this study
• Eastern Cooperative Oncology Group performance status 0-1
• Previous surgery or RFA to the liver is allowed; patients with history of chemoembolization or radio-labeled microspheres are excluded
• Life expectancy of >= 12 weeks
• Leukocytes >= 3,000/uL
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin =< ULN
• AST(SGOT)/ALT(SGPT)/Alkaline Phosphatase =< 2.5 X institutional ULN
• Creatinine < 2.0 mg/dL
• PT/PTT < 1.5 X ULN
• Women of childbearing potential (WOCBP) and sexually active males must agree to use an accepted and effective method of contraception prior to study entry and for the duration of the study; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal; even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy) should be considered to be of child bearing potential
• Patients must demonstrate ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have had chemotherapy (including targeted therapy i.e. cetuximab, panitumumab) or radiotherapy =< 4 weeks or treatment with bevacizumab =< 6 weeks prior to entering the study or those who have not recovered from acute adverse events due to agents administered more than 4 weeks earlier, with the exclusion of alopecia or neuropathy; patient with history of radiation to the liver including radio-labeled microspheres at any point in their past will be excluded
• Patients may not be receiving nor have received any other investigational agent =< 4 weeks prior to study registration
• Pregnant or nursing women may not participate in this trial because of the increased risk of fetal harm including death from the therapeutic agents
• Patients with known brain metastases are excluded from this study because of their poor prognosis and frequent development of progressive neurological dysfunction that would confound the evaluation of neurologic and other adverse events
• As patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, known HIV-positive patients and those with known hepatitis B or C are excluded from the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active bacterial infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with clinically evident ascites requiring medical management or paracentesis, or Childs-Pugh score B/C are not eligible
• Patients with evidence of other cancer within 5 years, excluding adequately treated basal cell carcinoma of the skin
• Patient with significant cardiac, renal or hematologic or pulmonary dysfunction
• Patients with previous chemoembolization to liver metastases
• Patients may not receive any other anticancer therapy while on study, including immunotherapy; patients may not receive any other clinical investigational drug

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fox Chase Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Efrat Dotan, MD

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Locations

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

10-002

Identifier Type: -

Identifier Source: org_study_id

NCI-2010-01114

Identifier Type: OTHER

Identifier Source: secondary_id

GI-063

Identifier Type: OTHER

Identifier Source: secondary_id