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 : June 29, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information
First Submitted Date  ICMJE December 7, 2017
First Posted Date  ICMJE December 8, 2017
Last Update Posted Date June 29, 2020
Actual Study Start Date  ICMJE June 24, 2019
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
Response rate RR [ Time Frame: at progression ]
The fraction of patients who experience a PR or CR using the study treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
  • Hepatic progression-free survival [ Time Frame: at progression ]
    The fraction of patients whose tumors in liver shrunk after therapy
  • Extra-hepatic progression-free survival [ Time Frame: at progression ]
    The fraction of patients whose tumors outside liver shrunk after therapy
  • Overall survival [ Time Frame: death ]
    Median amount of time subject survives after therapy
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Liver Metastases
  • Colorectal Adenocarcinoma
  • Colorectal Cancer With Hepatic Metastases
  • Colorectal Carcinoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: 1/Arm 1
HAIP chemotherapy + Systemic chemotherapy
Interventions:
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 7, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cathleen E Hannah (240) 409-8860 cathleen.hannah@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03366155
Other Study ID Numbers  ICMJE 180024
18-C-0024
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jonathan M Hernandez, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date April 21, 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP