Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03366155
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

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: OneRNA Drug: FUDR-Dex Drug: Oxaliplatin Drug: 5FU Drug: Irinotecan Procedure: HAIP installation Drug: cetuximab Device: Medtronic SynchroMed II Pump with Codman 3000 Constant Flow Pump Catheter 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.

- 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : June 24, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 30, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Floxuridine

Arm Intervention/treatment
Experimental: 1/Arm 1
HAIP chemotherapy + Systemic chemotherapy
Device: OneRNA
genomic test done on tumor and normal liver biopsy samples taken during baseline and end of treatment

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-Flouroucail + 400mg/m2, IV of Leucovorin

Drug: Irinotecan
150 mg/m2, IV

Procedure: HAIP installation
HAIP pump installation

Drug: cetuximab
500mg/m2,IV

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




Primary Outcome Measures :
  1. Response rate RR [ Time Frame: at progression ]
    The fraction of patients who experience a PR or CR using the study treatment


Secondary Outcome Measures :
  1. Hepatic progression-free survival [ Time Frame: at progression ]
    The fraction of patients whose tumors in liver shrunk after therapy

  2. Extra-hepatic progression-free survival [ Time Frame: at progression ]
    The fraction of patients whose tumors outside liver shrunk after therapy

  3. Overall survival [ Time Frame: death ]
    Median amount of time subject survives after therapy



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03366155


Contacts
Layout table for location contacts
Contact: Cathleen E Hannah (240) 409-8860 cathleen.hannah@nih.gov

Locations
Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Jonathan M Hernandez, M.D. National Cancer Institute (NCI)
Additional Information:
Publications:
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03366155    
Other Study ID Numbers: 180024
18-C-0024
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 21, 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Unresectable Liver Tumor
Response Rates
Progression-Free Survival
Patient Survival
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Adenocarcinoma
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Oxaliplatin
Irinotecan
Cetuximab
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological