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Hepatic Arterial Infusion Using Codman Catheter / Synchromed Pump for the Treatment of Unresectable Colorectal Cancer Liver Metastases or Unresectable Intrahepatic Cholangiocarcinoma

Trial Status: Active

This phase I trial studies the side effects of hepatic arterial infusion (HAI) using the Codman catheter / Synchromed pump in treating patients with colorectal cancer that has spread to the liver (metastases) and cannot be removed by surgery (unresectable) or unresectable intrahepatic cholangiocarcinoma. HAI is a procedure in which chemotherapy drugs are directly delivered to the liver through a pump that is surgically implanted into the liver. This approach can produce higher local concentrations of the infused drug with few systemic side effects. The manufacturer of the main pump device used for HAI terminated production in April 2018. Thus, alternate means of employing HAI need to be devised in order to continue offering this therapy. This trial may help researchers learn about the safety of HAI using a similar pump, the Synchromed II, combined with a Codman vascular catheter.

Inclusion Criteria

  • Histologically confirmed unresectable colorectal adenocarcinoma metastatic to the liver with no definitive clinical or radiographic evidence of extrahepatic disease. Clinical or radiographic evidence of metastatic disease to peri-hepatic lymph nodes will be allowed, provided it is amenable to resection. Up to 5 lung metastases are allowable, provided they are stable (or responding) in number and size for a minimum of 2-months of systemic chemotherapy and are amenable to stereotactic body radiation therapy (SBRT). OR Histologically confirmed unresectable intrahepatic cholangiocarcinoma, with presence of less than 70% liver involvement. Clinical or radiographic evidence of metastatic disease to peri-hepatic lymph nodes will be allowed, provided it is amenable to resection and there is no distant metastatic disease * The definition of resection is complex and consensus about resectability is typically made by a multi-disciplinary tumor board comprising hepatobiliary surgeons and radiology. Generally, a minimum of two contiguous liver segments are required in the future liver remnant, although substantially more liver volume may be required in the setting of pre-existing liver disease or extensive preoperative chemotherapy-related hepatocellular injury
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Absolute neutrophil count >= 1,500/mcL (=< 14 days prior to study enrollment)
  • Total bilirubin =< 1.5 mg/dL (=< 14 days prior to study enrollment)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 5 x institutional upper limit of normal (ULN) (=< 14 days prior to study enrollment)
  • Platelets >= 100,000/mcL (=< 14 days prior to study enrollment)
  • Creatinine < 1.5 mg/dL (=< 14 days prior to study enrollment)
  • Hemoglobin (HGB) >= 9 g/dL (=< 14 days prior to study enrollment)
  • International normalized ratio (INR) =< 1.5
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Prior chemotherapy is acceptable if last dose given >= 3 weeks prior to study enrollment
  • Any investigational agent is acceptable if last dose administered >= 3 months before study enrollment
  • Received a positive candidacy rating for hepatic arterial infusion pump (HAIP) chemotherapy as assessed by treating investigators via the modified Stanford Integrated Psychosocial Assessment for Transplant (mSIPAT) * Ratings indicating positive candidacy for HAIP chemotherapy are as follows: ** Patients with mSIPAT rating of “Excellent Candidate” are eligible ** Patients with mSIPAT rating of “Good Candidate” are eligible
  • Eligibility status of patients rated “Minimally Acceptable Candidate for HAIP Chemotherapy” on the mSIPAT will be at the discretion of the treating investigators. Treating investigator confirmed eligibility of any patient who received a rating of “Minimally Acceptable Candidate” on the mSIPAT

Exclusion Criteria

  • Presence of distant non-liver metastatic disease confirmed by radiographic evaluation. Clinical or radiographic evidence of metastatic disease to regional peri-hepatic lymph nodes will be allowed, provided it is amenable to resection. For the colorectal carcinoma only: Up to 5 lung metastases are allowable, provided they are stable (or responding) in number and size for a minimum of 2-months of systemic chemotherapy and are amenable to SBRT
  • Prior radiation to the liver, including external beam, SBRT, yttrium-90 (Y90). Prior radiation therapy to the pelvis is acceptable
  • Active infection, hepatic encephalopathy
  • Clinical evidence of portal hypertension (ascites, gastroesophageal varices or portal vein thrombosis) are exclusions. Note that surgically-related ascites does not exclude the patient
  • Female patients who are pregnant or lactating - or planning to become pregnant within 6 months after the end of the treatment (female patients of child-bearing potential must have negative pregnancy test prior to surgery)
  • If in the opinion of the treating investigator a patient has any serious medical problems which may preclude receiving this type of treatment
  • Patients with history or known presence of primary central nervous system (CNS) tumors, seizures not well-controlled with standard medical therapy. Patients with a history of stroke within 3 months or with substantial residual deficit, based on investigator discretion
  • Serious or non-healing active wound, ulcer, or bone fracture
  • Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the HAIP chemotherapy (i.e., investigational regimen)
  • Rating of “Poor/High Risk Candidate” on the modified Stanford Integrated Psychosocial Assessment of Transplant (mSIPAT) as assessed by treating investigator
  • Patients with psychiatric illness or social situations that would limit compliance with study requirements. Examples include: active substance abuse, active severe ethanol (ETOH) abuse, etc.
  • Inability to reliably commit to traveling to Lexington, Kentucky (KY) every 2 weeks for duration of the study treatment (6 months). Patient must have readily identifiable, reliable primary and back-up modes of transportation regardless of weather

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: ACTIVE
Contact: Michael J. Cavnar
Phone: 859-323-8920

PRIMARY OBJECTIVE:

I. Assess the safety of this hepatic artery infusion (HAI) pump/catheter combination in delivery of HAI therapy, concurrent with standard of care systemic chemotherapy in the population.

SECONDARY OBJECTIVES:

I. Feasibility of a hepatic artery infusion pump (HAIP) program in a predominantly rural patient catchment area.

II. Measure overall response rate to standard hepatic artery infusion chemotherapy (floxuridine [FUDR]) combined with standard systemic chemotherapy (tailored to primary disease) measured via Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, and determine rate of conversion to resection at 6-months.

EXPLORATORY OBJECTIVES:

I. Evaluate plasma concentrations of FUDR after hepatic arterial administration.

II. Estimate the relative contribution of intravenous administration of fluorouracil (5-FU) and hepatic artery administration of FUDR on plasma FUDR concentrations.

III. Develop a population pharmacokinetic model for 5-FU, FUDR and 5-fluorodeoxyuridine monophosphase (FdUMP).

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I (UNRESECTABLE METASTATIC COLON CANCER): Patients undergo surgery for implantation of the HAI pump and catheter. Beginning no sooner than 14 days after surgery, patients receive floxuridine and dexamethasone via HAI pump on day 1. Patients also receive 1 of 3 chemotherapy regimens per oncologist discretion on day 15 of cycle 1 and on days 1 and 15 of subsequent cycles: 1) FOLFIRI consisting of leucovorin calcium intravenously (IV) via bolus injection or over 10-120 minutes, fluorouracil IV, and irinotecan IV over 90 minutes, 2) FOLFOX consisting of leucovorin calcium IV via bolus injection or over 10-120 minutes, fluorouracil IV, and oxaliplatin IV over 2-6 hours, or 3) irinotecan IV over 90 minutes and oxaliplatin IV over 2-6 hours. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

ARM II (UNRESECTABLE INTRA-HEPATIC CHOLANGIOCARCINOMA): Patients undergo surgery for implantation of the HAI pump and catheter. Beginning no sooner than 14 days after surgery, patients receive floxuridine and dexamethasone via HAI pump on day 1. Patients also receive 1 of 2 chemotherapy regimens per oncologist discretion on day 15 of cycle 1 and on days 1 and 15 of subsequent cycles: 1) gemcitabine IV over 30 minutes and oxaliplatin IV over 2-6 hours or 2) gemcitabine IV over 30 minutes alone. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then up to 3 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Kentucky / Markey Cancer Center

Principal Investigator
Michael J. Cavnar

  • Primary ID MCC-19-GI-109-PMC
  • Secondary IDs NCI-2020-03203, 2019-130, 55664
  • Clinicaltrials.gov ID NCT04276090