Clinical Trials /

Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver

NCT03366155

Description:

Background: Many people with colorectal cancer get liver metastases. Standard treatment for this is a combination of chemotherapy drugs. Directing the chemotherapy to the liver may be effective. A device that does this a pump that delivers drugs over 2 weeks at constant rate into the hepatic artery. The person s body temperature causes the drug to flow from the pump. Researchers want to see if this helps people with colorectal metastases to the liver. Objective: To study the effectiveness of a hepatic artery infusion pump at treating colorectal metastases to the liver. Eligibility: Adults at least 18 years old with colorectal metastases to the liver Design: Participants will be screened with: Medical history Physical exam Heart, blood, and urine tests Scans Participants will stay in the hospital a few days. A small plastic tube (catheter) will be inserted in an artery into the liver. The catheter will be attached to the pump. That will lie under the skin on the abdomen. It will be small and participants will be able to feel it. Participants will get treatment in 28-day cycles. Every Day 1, they will have physical exam, symptom review, and blood tests. Every 2 weeks, they will come to the clinic to get chemotherapy by a catheter or port. Every 12 weeks, they will have a scan. Tissue samples may be taken during the study. When they finish the drug, participants may have the pump removed. They will repeat the Day 1 tests. They will be called every 6 months to see how they are doing. Sponsoring Institute: National Cancer Institute

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver
  • Official Title: A Single-Arm Phase II Study of Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver

Clinical Trial IDs

  • ORG STUDY ID: 180024
  • SECONDARY ID: 18-C-0024
  • NCT ID: NCT03366155

Conditions

  • Colorectal Cancer
  • Liver Metastases
  • Colorectal Adenocarcinoma
  • Colorectal Cancer With Hepatic Metastases
  • Colorectal Carcinoma

Interventions

DrugSynonymsArms
FUDR-Dex1/Arm 1
Oxaliplatin1/Arm 1
5FU1/Arm 1
Irinotecan1/Arm 1
cetuximab1/Arm 1

Purpose

Background: Many people with colorectal cancer get liver metastases. Standard treatment for this is a combination of chemotherapy drugs. Directing the chemotherapy to the liver may be effective. A device that does this a pump that delivers drugs over 2 weeks at constant rate into the hepatic artery. The person s body temperature causes the drug to flow from the pump. Researchers want to see if this helps people with colorectal metastases to the liver. Objective: To study the effectiveness of a hepatic artery infusion pump at treating colorectal metastases to the liver. Eligibility: Adults at least 18 years old with colorectal metastases to the liver Design: Participants will be screened with: Medical history Physical exam Heart, blood, and urine tests Scans Participants will stay in the hospital a few days. A small plastic tube (catheter) will be inserted in an artery into the liver. The catheter will be attached to the pump. That will lie under the skin on the abdomen. It will be small and participants will be able to feel it. Participants will get treatment in 28-day cycles. Every Day 1, they will have physical exam, symptom review, and blood tests. Every 2 weeks, they will come to the clinic to get chemotherapy by a catheter or port. Every 12 weeks, they will have a scan. Tissue samples may be taken during the study. When they finish the drug, participants may have the pump removed. They will repeat the Day 1 tests. They will be called every 6 months to see how they are doing. Sponsoring Institute: National Cancer Institute

Detailed Description

      Background:

        -  Nearly 60% of patients with colorectal cancers will develop liver metastases over the
           course of their disease.

        -  Of patients with metastatic colorectal cancer, the liver will be the sole site of
           recurrence or the survival-limiting site of disease for 20%.

        -  Liver directed therapy, which has taken many forms over the last several decades, is a
           potential means to prolong survival for properly selected patients and delay progression
           at that site.

        -  Hepatic artery infusion of floxuridine (FUDR) via an implantable hepatic artery infusion
           pump (HAIP) induces objective clinical response rates of nearly 50% in heavily
           pretreated patients with metastatic colorectal cancer to the liver.

        -  The identification of patients likely to respond to HAIP and those likely to suffer
           pumprelated adverse events is currently unknown, and has limited the wide-spread
           adoption of this otherwise well tolerated intervention.

      Objective:

      -To assess the safety of hepatic artery infusion therapy using the Medtronic pump with the

      Codman catheter.

      - Determine the response rate in patients with unresectable metastatic colorectal cancer
      treated with HAIP chemotherapy as measured by RECIST.

      Eligibility:

        -  Histologically or cytologically confirmed colorectal adenocarcinoma metastatic to the
           liver.

        -  Patients with liver metastases not amenable to resection to No Evidence of Disease (NED)
           in one stage.

        -  Patients must have received systemic chemotherapy.

        -  Age greater than or equal to 18 years.

      Design:

      - Single arm, phase II study of HAIP chemotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
1/Arm 1ExperimentalHAIP chemotherapy + Systemic chemotherapy
  • FUDR-Dex
  • Oxaliplatin
  • 5FU
  • Irinotecan
  • cetuximab

Eligibility Criteria

        -  INCLUSION CRITERIA:

          -  Patients must have histologically or cytologically confirmed diagnosis of colorectal
             adenocarcinoma, confirmed by the Laboratory of Pathology, NCI.

          -  Patients must have measurable liver metastatic disease.

          -  Patients must have progressed on, been intolerant of or have residual disease after
             oxaliplatin- or irinotecan-containing, fluorouracil-based, chemotherapeutic regimen.

          -  Age greater than or equal to 18 years.

          -  ECOG performance status less than or equal to 1

          -  Patients must have adequate organ and marrow function as defined below:

               -  leukocytes > 3,000/mcL

               -  absolute neutrophil count > 1,500/mcL

               -  platelets > 90,000/mcL

               -  total bilirubin < 1.5 X institutional upper limit of normal

               -  AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal

               -  creatinine within normal institutional limits OR eGFR within normal as predicted
                  by the CKD-EPI equation > 60 mL/min/1.73 m2.

          -  The hepatic artery infusion pump chemotherapy has potential teratogenic and/or
             abortifacient effects. For this reason, women of child-bearing potential and men must
             agree to use adequate contraception (hormonal or barrier method of birth control;
             abstinence) prior to study entry, for the duration of study participation and for 3
             months after completion of study treatment. Should a woman become pregnant or suspect
             she is pregnant while she or her partner is participating in this study, she should
             inform her treating physician immediately.

          -  Arterial anatomy on CT angiogram amenable to placement of the HAIP.

          -  Ability of subject to understand and the willingness to sign a written informed
             consent document.

          -  HIV-positive patients may be considered for this study only after consultation with an
             HIV trained physician.

        EXCLUSION CRITERIA:

          -  Patients with liver metastases amenable to resection to No Evidence of Disease (NED)
             in one stage.

          -  Patients who are receiving any other investigational agents.

          -  Patients with incontrovertible radiographic evidence of disease outside of the
             colon/rectum (primary) and liver given unlikelihood of benefit from liver-directed
             therapy.

        Note: The exception to this exclusion is patients with fewer than five lung lesions greater
        than 1 cm that have not increased in size by more than 10% over a 4-month period of time,
        and are amenable to resection should subsequent problematic growth occur. Lesions less than
        1 cm are indeterminant as far as etiology is concerned and will be ignored. Patients with
        liver metastases and oligometastatic lung lesions (we define oligometastatic as less than 5
        amen ble to thoracoscopic removal) are still likely to benefit from liver directed therapy.

          -  Patients who have undergone extra-hepatic metastasectomy and have a documented
             disease-free interval less than or equal to 4 months.

          -  MSI-high patients who need to be treated with a check-point inhibitors

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements. This also includes any condition, including the presence of
             laboratory abnormalities, which in the opinion of the Principal Investigator places
             the subject at unacceptable risk if they were to participate in the study or confounds
             the ability to interpret data from the study.

          -  Active concurrent malignancies within the last five years other than colorectal
             primary except basal cell skin carcinoma and thyroid carcinoma.

          -  Prior radiation to liver.

          -  Pregnant women are excluded from this study because of the potential for teratogenic
             or abortifacient effects of the HAIP chemotherapy. Because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with HAIP, breastfeeding should be discontinued if the mother is treated. These
             potential risks may also apply to other agents used in this study.

          -  Patients with active Hepatitis B or C infection because of the potential for increased
             liver toxicity given the damaging effects of the virus.

          -  History of allergic reactions attributed to compounds of similar chemical composition
             to FUDR or heparin.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate RR
Time Frame:at progression
Safety Issue:
Description:The fraction of patients who experience a PR or CR using the study treatment

Secondary Outcome Measures

Measure:Hepatic progression-free survival
Time Frame:at progression
Safety Issue:
Description:The fraction of patients whose tumors in liver shrunk after therapy
Measure:Extra-hepatic progression-free survival
Time Frame:at progression
Safety Issue:
Description:The fraction of patients whose tumors outside liver shrunk after therapy
Measure:Overall survival
Time Frame:death
Safety Issue:
Description:Median amount of time subject survives after therapy

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • Unresectable Liver Tumor
  • Response Rates
  • Progression-Free Survival
  • Patient Survival

Last Updated

October 29, 2019