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

Phase 1

Terminated

• Conditions: Recurrent Colon Cancer; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer; Liver Metastases; Recurrent Rectal Cancer
• Interventions: Combination Product: irinotecan-eluting beads; Procedure: hepatic artery embolization

• Registration Number: NCT01285102
• Lead Sponsor: Fox Chase Cancer Center

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.

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2011-01-26
• Study First Submitted QC: 2011-01-26
• Study First Posted: 2011-01-27
• Primary Completion: 2011-12
• Study Completion: 2013-01
• Results First Submitted: 2021-11-02
• Status Verified: 2021-12
• Results First Submitted QC: 2021-12-17
• Last Update Submitted: 2021-12-17
• Results First Posted: 2021-12-20
• Last Update Posted: 2021-12-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	hepatic artery embolization	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.
Arm I	irinotecan-eluting beads	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.

Primary Outcome Measures

Name	Time	Method
Time to Progression	Duration of time from start of treatment to progression
Patient Tolerance and Toxicity Profile	First treatment then 30 days after completion of treatment then every 3 months for 2 years
Overall Survival	30 days after completion of treatment then every 3 months for 2 years

Trial Locations

Locations (1)

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States