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Trial record 20 of 168 for:    colon cancer AND Colorectal Neoplasms | ( Map: New Jersey, United States )

Hepatic Arterial Infusion With Floxuridine and Dexamethasone Combined With Combination Chemotherapy in Treating Patients With Colorectal Cancer That Has Spread to the Liver

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ClinicalTrials.gov Identifier: NCT00492999
Recruitment Status : Active, not recruiting
First Posted : June 27, 2007
Last Update Posted : February 5, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE June 25, 2007
First Posted Date  ICMJE June 27, 2007
Last Update Posted Date February 5, 2019
Actual Study Start Date  ICMJE May 2007
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
Resectability rate [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 25, 2007)
Resectability rate
Change History Complete list of historical versions of study NCT00492999 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
  • Antitumor activity [ Time Frame: 2 years ]
  • Response rate [ Time Frame: 2 years ]
  • Median time to progression [ Time Frame: 2 years ]
  • Survival [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2007)
  • Antitumor activity
  • Response rate
  • Median time to progression
  • Survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hepatic Arterial Infusion With Floxuridine and Dexamethasone Combined With Combination Chemotherapy in Treating Patients With Colorectal Cancer That Has Spread to the Liver
Official Title  ICMJE A Phase II Study of the Rate of Conversion to Complete Resection in Patients With Initially Inoperable Hepatic-Only Metastases From Colorectal Cancer After Treatment With Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Best Systemic Chemotherapy
Brief Summary

RATIONALE: Hepatic arterial infusion uses a catheter to carry tumor-killing substances directly into the liver. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving floxuridine and dexamethasone directly into the arteries around the tumor together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well hepatic arterial infusion with floxuridine and dexamethasone works when given together with combination chemotherapy in treating patients with colorectal cancer that has spread to the liver.

Detailed Description

OBJECTIVES:

Primary

  • Assess the rate of conversion to complete resection in patients with initially unresectable colorectal cancer metastatic to the liver treated with hepatic arterial infusion comprising floxuridine and dexamethasone in combination with systemic irinotecan hydrochloride and either oxaliplatin or leucovorin calcium/fluorouracil.

Secondary

  • Evaluate the time to progression in patients treated with this regimen.
  • Evaluate disease-free survival of patients treated with this regimen.
  • Evaluate overall survival of patients treated with this regimen.
  • Determine the response rate (complete, partial, and moderate response) in patients treated with this regimen.
  • Evaluate the safety profile and tolerability of this regimen in these patients.
  • Assess the expression pattern of the VEGF receptor VEGFR1, VEGFR2, and VEGFR3 and their cognate ligands (i.e., VEGF-A, VEGF-B, VEGF-C, VEGF-D, and P1GF) in patients treated with this regimen.
  • Correlate circulating angiogenic markers with tumor resectability, disease progression, and patient survival.
  • Procure normal and diseased liver tissue for evaluation of thymidylate synthase, p53 gene, p21, topoisomerase 1, dihydropyrimidine dehydrogenase, and excision repair cross-complementing gene levels.
  • Assess the expression pattern of tissue factor (TF) and explore its correlation with the TF receptors PAR-1, PAR-2, TF regulators PTEN, k-ras, b- raf, p53, and outcome.(Closed as of 11/30/10)
  • Assess the prognostic and predictive role of preoperative, pretreatment, and during treatment serum TF in regards to outcome (progression-free survival and overall survival) and response to treatment with this regimen and to salvage treatments such as EGFR-inhibitors.(Closed as of 11/30/10)

OUTLINE: This is an open-label, nonrandomized study. Patients are assigned to 1 of 2 treatment groups according to receipt of more than 2 prior courses of oxaliplatin (no vs yes).

  • Group 1 (no more than 2 prior courses of oxaliplatin): Patients receive hepatic arterial infusion (HAI) therapy comprising floxuridine and dexamethasone continuously on days 1-14. Patients also receive oxaliplatin IV over 2 hours and irinotecan hydrochloride IV over 30 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Group 2 (more than 2 prior courses of oxaliplatin): Patients receive HAI therapy as in group 1. Patients also receive irinotecan hydrochloride IV over 30 minutes and leucovorin calcium IV over 30 minutes on days 1 and 15 and fluorouracil IV continuously over 48 hours on days 1, 2, 15, and 16. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

In both groups, patients may undergo complete resection of liver metastases after completion of at least 3 courses of therapy.

Some patients undergo blood and tissue collection periodically for correlative and immunological studies. Samples are analyzed for VEGF receptor VEGFR1, VEGFR2, VEGFR3, thymidylate synthase, p53, p21, topoisomerase 1, dihydropyrimidine dehydrogenase, and excision repair cross-complementing gene levels.

After completion of study treatment, patients are followed every 3 months for 2 years, every 4 months for 3 years, and then annually thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Metastatic Cancer
Intervention  ICMJE
  • Drug: dexamethasone
    Given by hepatic arterial infusion
  • Drug: floxuridine
    Given by hepatic arterial infusion
  • Drug: fluorouracil
    Given IV
  • Drug: irinotecan hydrochloride
    Given IV
  • Drug: leucovorin calcium
    Given IV
  • Drug: oxaliplatin
    Given IV
Study Arms  ICMJE
  • Experimental: Group 1
    Patients receive hepatic arterial infusion (HAI) therapy comprising floxuridine and dexamethasone continuously on days 1-14. Patients also receive oxaliplatin IV over 2 hours and irinotecan hydrochloride IV over 30 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: dexamethasone
    • Drug: floxuridine
    • Drug: irinotecan hydrochloride
    • Drug: oxaliplatin
  • Experimental: Group 2
    Patients receive HAI therapy as in group 1. Patients also receive irinotecan hydrochloride IV over 30 minutes and leucovorin calcium IV over 30 minutes on days 1 and 15 and fluorouracil IV continuously over 48 hours on days 1, 2, 15, and 16. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: dexamethasone
    • Drug: floxuridine
    • Drug: fluorouracil
    • Drug: irinotecan hydrochloride
    • Drug: leucovorin calcium
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 24, 2011)
64
Original Enrollment  ICMJE
 (submitted: June 25, 2007)
49
Estimated Study Completion Date  ICMJE May 2020
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal adenocarcinoma metastatic to the liver

    • Previously treated or untreated disease
    • No clinical or radiographic evidence of extrahepatic disease
  • Primary tumor may be present at study registration provided it is not obstructing the intestinal lumen or is significantly bleeding

    • If present, the primary tumor will be resected at the time of pump placement
  • Must have inoperable liver metastases confirmed by 2-3 hepatobiliary surgeons and the assigned radiologist

    • Liver metastases < 70% of the liver parenchyma
    • Inoperable liver metastases is defined by one of the following:

      • More than 6 metastases in a single lobe with one lesion ≥ 5 cm
      • At least 6 metastases distributed diffusely in both lobes of the liver
      • When a margin-negative resection would require resection of all three hepatic veins, both portal veins, or the retrohepatic vena cava
      • Requires a resection that leaves < 2 hepatic segments (not including the caudate lobe) behind with adequate arterial or portal inflow, venous outflow, and biliary drainage
  • No ascites or hepatic encephalopathy
  • No history of primary CNS tumors

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • WBC ≥ 3,000/mm^3
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • INR < 1.5
  • Hemoglobin ≥ 9 g/dL
  • Creatinine ≤ 1.5 mg/dL
  • Total bilirubin ≤ 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Physically able to tolerate major partial hepatectomy
  • No active infection
  • No concurrent active malignancies, except potentially resectable primary colorectal tumor
  • No bleeding diathesis or coagulopathy
  • No history of serious systemic disease, including any of the following:

    • Myocardial infarction within the past 6 months
    • Uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg on medication)
    • Unstable angina
    • New York Heart Association class II-IV congestive heart failure
    • Unstable symptomatic arrhythmia requiring medication

      • Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed
    • Peripheral vascular disease ≥ grade 2
  • No serious or nonhealing active wound, ulcer, or bone fracture
  • No history of seizures not well controlled with standard medical therapy
  • No stroke or transient ischemic attack within the past 6 months
  • No concurrent obstruction of the gastrointestinal or genitourinary tract

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since prior radiotherapy to the pelvis
  • Prior chemotherapy allowed
  • No prior radiotherapy, hepatic thermal ablation, or resection (other than biopsy) to the liver
  • No prior floxuridine
  • No prior hepatic arterial infusion
  • No concurrent chronic aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function
  • No other concurrent investigational agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00492999
Other Study ID Numbers  ICMJE 06-075
MSKCC-06075
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Michael D'Angelica, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: Nancy E. Kemeny, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date February 2019

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