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

This study has been terminated.
(This study was closed early by the DSMB due to increased toxicity.)
Sponsor:
Information provided by (Responsible Party):
Fox Chase Cancer Center
ClinicalTrials.gov Identifier:
NCT01285102
First received: January 26, 2011
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
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
Device: irinotecan-eluting beads
Procedure: hepatic artery embolization
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Drug-eluting Irinotecan Beads (DEBIRI) in Refractory Metastatic Colorectal Cancer With Liver-only or Liver-predominant Disease

Resource links provided by NLM:


Further study details as provided by Fox Chase Cancer Center:

Primary Outcome Measures:
  • Time to progression [ Time Frame: Duration of time from start of treatment to progression ] [ Designated as safety issue: No ]
  • Patient tolerance and toxicity profile [ Time Frame: First treatment then 30 days after completion of treatment then every 3 months for 2 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 30 days after completion of treatment then every 3 months for 2 years ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: October 2010
Study Completion Date: January 2013
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Device: 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
Other Name: DEBIRI
Procedure: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  • 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

  • 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
  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: NCT01285102

Locations
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
Fox Chase Cancer Center
Investigators
Principal Investigator: Efrat Dotan, MD Fox Chase Cancer Center
  More Information

No publications provided

Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT01285102     History of Changes
Other Study ID Numbers: FCCC IRB 10-002, NCI-2010-01114
Study First Received: January 26, 2011
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystadenocarcinoma
Liver Neoplasms
Neoplasm Metastasis
Rectal Neoplasms
Colonic Neoplasms
Adenocarcinoma
Adenocarcinoma, Mucinous
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Neoplastic Processes
Pathologic Processes
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Cystic, Mucinous, and Serous
Irinotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014