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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT03366155

Collaborator

(none)

Enrollment

Location

Arm

78.2

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

Sponsoring Institute: National Cancer Institute

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Liver Metastases Colorectal Adenocarcinoma Colorectal Cancer With Hepatic Metastases Colorectal Carcinoma	Device: Codman 3000 constant flow pump catheter Drug: Panitumumab Drug: FUDR-Dex Drug: Oxaliplatin Drug: 5FU Drug: Irinotecan Procedure: HAIP installation Drug: cetuximab Device: Medtronic SynchroMed II Pump	Phase 2

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.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 24, 2019

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1/ Arm 1 HAIP chemotherapy + Systemic chemotherapy	Device: Codman 3000 constant flow pump catheter implanted Medtronic SynchroMed II Pump with codman 3000 Constant Flow Pump Catheter Drug: Panitumumab 6 mg/kg, IV Drug: FUDR-Dex 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) Drug: Oxaliplatin 85 mg/m2, IV Drug: 5FU 2000 mg/m2, IV 46-hour infusion of 5-Fluorouracil + 400 mg/m2, IV of Leucovorin Drug: Irinotecan 150 mg/m2, IV Procedure: HAIP installation HAI pump installation Drug: cetuximab 500 mg/m2, IV Device: Medtronic SynchroMed II Pump implanted Medtronic SynchroMed II Pump with Codman 3000 Constant Flow Pump Catheter

Arm

Intervention/Treatment

Experimental: 1/ Arm 1

HAIP chemotherapy + Systemic chemotherapy

Device: Codman 3000 constant flow pump catheter

implanted Medtronic SynchroMed II Pump with codman 3000 Constant Flow Pump Catheter

Drug: Panitumumab

6 mg/kg, IV

Drug: FUDR-Dex

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)

Drug: Oxaliplatin

85 mg/m2, IV

Drug: 5FU

2000 mg/m2, IV 46-hour infusion of 5-Fluorouracil + 400 mg/m2, IV of Leucovorin

Drug: Irinotecan

150 mg/m2, IV

Procedure: HAIP installation

HAI pump installation

Drug: cetuximab

500 mg/m2, IV

Device: Medtronic SynchroMed II Pump

implanted Medtronic SynchroMed II Pump with Codman 3000 Constant Flow Pump Catheter

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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.