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

Primary Purpose

Colorectal Cancer, Liver Metastases, Colorectal Adenocarcinoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Codman 3000 constant flow pump catheter
Panitumumab
FUDR-Dex
Oxaliplatin
5FU
Irinotecan
HAIP installation
cetuximab
Medtronic SynchroMed II Pump
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring Unresectable Liver Tumor, Response Rates, Progression-Free Survival, Patient Survival

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • INCLUSION CRITERIA:
  • Patients must have histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma.
  • 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.
  • Patients must agree to co-enroll on the Surgical Oncology Program s tissue collection protocol 13C0176, 'Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors'

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.

Sites / Locations

  • National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1/ Arm 1

Arm Description

HAIP chemotherapy + Systemic chemotherapy

Outcomes

Primary Outcome Measures

Response rate (RR)
The fraction of patients who experience a PR or CR using the study treatment

Secondary Outcome Measures

Overall survival
Median amount of time subject survives after therapy
Hepatic progression-free survival
The fraction of patients whose tumors in liver shrunk after therapy
Extra-hepatic progression-free survival
The fraction of patients whose tumors outside liver shrunk after therapy

Full Information

First Posted
December 7, 2017
Last Updated
September 15, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03366155
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 14, 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 24, 2019 (Actual)
Primary Completion Date
December 31, 2029 (Anticipated)
Study Completion Date
December 30, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.
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 pre-treated 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. - To 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Liver Metastases, Colorectal Adenocarcinoma, Colorectal Cancer With Hepatic Metastases, Colorectal Carcinoma
Keywords
Unresectable Liver Tumor, Response Rates, Progression-Free Survival, Patient Survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1/ Arm 1
Arm Type
Experimental
Arm Description
HAIP chemotherapy + Systemic chemotherapy
Intervention Type
Device
Intervention Name(s)
Codman 3000 constant flow pump catheter
Intervention Description
implanted Medtronic SynchroMed II Pump with codman 3000 Constant Flow Pump Catheter
Intervention Type
Drug
Intervention Name(s)
Panitumumab
Intervention Description
6 mg/kg, IV
Intervention Type
Drug
Intervention Name(s)
FUDR-Dex
Intervention Description
HAIP will be filled with mixture of Floxuridine and Dexamethasone. Pump will perfuse drugs to liver for 14 days. Floxuridine (0.12 mg/kg X pump volume X pump flow rate),Dexamethasone (1 mg/day X pump volume (30) X pump flow rate)
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
85 mg/m2, IV
Intervention Type
Drug
Intervention Name(s)
5FU
Intervention Description
2000 mg/m2, IV 46-hour infusion of 5-Fluorouracil + 400 mg/m2, IV of Leucovorin
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
150 mg/m2, IV
Intervention Type
Procedure
Intervention Name(s)
HAIP installation
Intervention Description
HAI pump installation
Intervention Type
Drug
Intervention Name(s)
cetuximab
Intervention Description
500 mg/m2, IV
Intervention Type
Device
Intervention Name(s)
Medtronic SynchroMed II Pump
Intervention Description
implanted Medtronic SynchroMed II Pump with Codman 3000 Constant Flow Pump Catheter
Primary Outcome Measure Information:
Title
Response rate (RR)
Description
The fraction of patients who experience a PR or CR using the study treatment
Time Frame
at progression
Secondary Outcome Measure Information:
Title
Overall survival
Description
Median amount of time subject survives after therapy
Time Frame
death
Title
Hepatic progression-free survival
Description
The fraction of patients whose tumors in liver shrunk after therapy
Time Frame
at progression
Title
Extra-hepatic progression-free survival
Description
The fraction of patients whose tumors outside liver shrunk after therapy
Time Frame
at progression

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Patients must have histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma. 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 after completion of study treatment : 3 months after the last study drug for men; 6 months after the last study drug for women. 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. Patients must agree to co-enroll on the Surgical Oncology Program s tissue collection protocol 13C0176, 'Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors' 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 amenable 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 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, breast-feeding should be discontinued if the mother is treated. These potential risks may also apply to other agents used in this study. Lactating women must-not breastfeed during study treatment and until at least 7 days after the final dose of study drug(s). 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kathleen M Smith, R.N.
Phone
(240) 858-3531
Email
kathleen.smith3@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Jonathan M Hernandez, M.D.
Phone
(240) 760-6072
Email
jonathan.hernandez@nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan M Hernandez, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
Phone
888-624-1937

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
.All IPD recorded in the medical record will be shared with intramural investigators upon request.
IPD Sharing Time Frame
Clinical data available during the study and indefinitely.
IPD Sharing Access Criteria
Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.
Citations:
PubMed Identifier
23771246
Citation
Ammori JB, Kemeny NE, Fong Y, Cercek A, Dematteo RP, Allen PJ, Kingham TP, Gonen M, Paty PB, Jarnagin WR, D'Angelica MI. Conversion to complete resection and/or ablation using hepatic artery infusional chemotherapy in patients with unresectable liver metastases from colorectal cancer: a decade of experience at a single institution. Ann Surg Oncol. 2013 Sep;20(9):2901-7. doi: 10.1245/s10434-013-3009-3. Epub 2013 Jun 15.
Results Reference
background
PubMed Identifier
24646562
Citation
D'Angelica MI, Correa-Gallego C, Paty PB, Cercek A, Gewirtz AN, Chou JF, Capanu M, Kingham TP, Fong Y, DeMatteo RP, Allen PJ, Jarnagin WR, Kemeny N. Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes. Ann Surg. 2015 Feb;261(2):353-60. doi: 10.1097/SLA.0000000000000614.
Results Reference
background
PubMed Identifier
24154839
Citation
Cercek A, D'Angelica M, Power D, Capanu M, Gewirtz A, Patel D, Allen P, Fong Y, DeMatteo RP, Jarnagin WR, Kemeny NE. Floxuridine hepatic arterial infusion associated biliary toxicity is increased by concurrent administration of systemic bevacizumab. Ann Surg Oncol. 2014 Feb;21(2):479-86. doi: 10.1245/s10434-013-3275-0. Epub 2013 Oct 24.
Results Reference
background
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2018-C-0024.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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