Clinical Trials /

A Study of Systemic Chemotherapy With/Without HAI in Patients With Initially Unresectable Colorectal Liver Metastasis

NCT02102789

Description:

The primary objective of this study is to determine whether systemic chemotherapy combined with hepatic arterial infusion with floxuridine and dexamethasone can increase the complete resection rate (R0) and improve the overall survival in patients with initially unresectable colorectal liver metastasis.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Systemic Chemotherapy With/Without HAI in Patients With Initially Unresectable Colorectal Liver Metastasis
  • Official Title: Systemic Chemotherapy With or Without Hepatic Arterial Infusion With Floxuridine in Patients With Initially Unresectable Colorectal Liver Metastasis: A Prospective, Randomised, Controlled Study

Clinical Trial IDs

  • ORG STUDY ID: Frozen-2
  • NCT ID: NCT02102789

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
mFOLFOX6Oxaliplatin, Leucovorin, 5-fluorouracilSystemic chemotherapy
HAIfloxuridine (FUDR), dexamethasoneSystemic chemotherapy combined with HAI

Purpose

The primary objective of this study is to determine whether systemic chemotherapy combined with hepatic arterial infusion with floxuridine and dexamethasone can increase the complete resection rate (R0) and improve the overall survival in patients with initially unresectable colorectal liver metastasis.

Detailed Description

      Recent studies and our experience have proved the efficacy and safety of systemic
      chemotherapy combined with hepatic arterial infusion (HAI) with floxuridine and dexamethasone
      in patients with initially unresectable colorectal liver metastasis. However, most of them
      are retrospective studies, phase I or II clinical researches, which could not provide
      high-level evidence. Therefore, we designed this study to determine whether systemic
      chemotherapy combined with HAI can increase the complete resection rate (R0) and improve the
      overall survival in patients with initially unresectable colorectal liver metastasis.
    

Trial Arms

NameTypeDescriptionInterventions
Systemic chemotherapyExperimentalPatients will receive mFOLFOX6 every 28 days: Oxaliplatin 85 mg/m2 IV over 3 hours on Day 1, 15; Leucovorin (l-LV) 200mg/m2 IV over 2 hours on Day 1, 15; followed by 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1, 15.
  • mFOLFOX6
Systemic chemotherapy combined with HAIExperimentalPatients will receive mFOLFOX6+HAI every 28 days: Oxaliplatin 85 mg/m2 IV over 3 hours on Day 1, 15; Leucovorin (l-LV) 200mg/m2 IV over 2 hours on Day 1, 15; followed by 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1, 15. 0.12 mg/kg/day floxuridine (FUDR) and 25 mg dexamethasone in normal saline to a total volume of 300 ml will be administered through the HAI pump. This will be repeated on Day 1 of each 28-day cycle. FUDR will be administered through a 14-day continuous infusion with the HAI pump.
  • mFOLFOX6
  • HAI

Eligibility Criteria

        Inclusion Criteria:

          -  Age: 18-70 years old

          -  Histologically confirmed colorectal adenocarcinoma

          -  Radiologically or pathologically confirmed diagnosis of colorectal liver metastasis

          -  Initially unresectable colorectal liver metastasis confirmed by the multidisciplinary
             team (MDT)

          -  With no prior treatment for liver metastasis, including chemotherapy, operation,
             radiotherapy, transcatheter hepatic arterial chemoembolization (TACE) and targeted
             therapy

          -  Without extra-hepatic metastasis confirmed by CT, MRI or PET/CT (if necessary)
             scanning

          -  With adequate bone marrow function: platelets ≥ 90 x 109/L; white blood cells ≥
             3×109/L; absolute neutrophil count (ANC) ≥ 1.5 x 109/L

          -  Serum bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 5 x ULN

          -  Patient has no ascites and with adequate blood coagulation function, albumin ≥ 35 g/L

          -  Grade A level of Child-Push Liver Function

          -  Creatinine ≤ 1× ULN, or Calculated Creatinine Clearance >50ml/min (Cockcroft-Gault
             Equation)

          -  ECOG performance status of 0-2

          -  Life expectancy ≥ 3 months

          -  Not appropriate for anti-EGFR or any other targeted therapy (with KRAS mutation or
             could not afford it)

          -  Patients have provided a signed Informed Consent Form

          -  With good compliance

        Exclusion Criteria:

          -  With any extra-hepatic metastasis and/or primary tumor recurrence

          -  Severe arterial embolism or ascites

          -  With hemorrhagic tendency or coagulation disorders

          -  Hypertensive crisis or hypertensive encephalopathy

          -  Severe and uncontrolled systemic complications such as infections or diabetes

          -  Serious cardiovascular diseases such as cerebrovascular accident (within 6 months
             before enrollment), myocardial infarction (within 6 months before enrollment),
             uncontrolled hypertension even with appropriate drug intervention, unstable angina
             pectoris, congestive heart failure (NYHA 2-4 degree), arrhythmia that needs medication
             intervention

          -  Patient who has suffered from central nervous system diseases such as primary brain
             tumor, uncontrolled epilepsy even with standard treatment, any brain metastasis or
             stroke

          -  Patient who has a concurrent malignancy or has a malignancy within 5 years before
             study enrollment, (with the exception of radically resected skin basal cell carcinoma
             or cervical carcinoma in situ)

          -  Patient who has received any investigational antineoplastic agent within 28 days
             before the enrollment

          -  Any residual toxicity from prior chemotherapy (with the exception of alopecia), such
             as grade 2 or more sensory peripheral neuropathy (NCI CTC v3.0), oxaliplatin-based
             regimen will not be considered

          -  Patient who is allergic to oxaliplatin, leucovorin, 5-Fluorouracil, floxuridine or
             dexamethasone

          -  Pregnant or lactating women

          -  Patient who does not use or refuses to take any appropriate contraceptive measures
             (intrauterine contraceptive ring, barrier contraception combined with spermicidal gel
             or sterilization operation), including women of childbearing age (within 2 years after
             the last menstrual period) and men who are with possible fertility

          -  Unable or unwilling to comply with the research plan

          -  The existence of any other disease, dysfunction caused by metastatic lesions, or
             suspicious disease found on the regular examination, which indicating
             contraindications to the use of study drugs or may bring high risks of treatment
             related complications
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete resection rates (R0 resection rates) (defined as no macroscopic or microscopic residual tumor) of both arms
Time Frame:Up to 2-4 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rates (ORR) of both arms
Time Frame:Up to 4-8 monthes
Safety Issue:
Description:
Measure:R1 resection rates (with microscopic residual tumor) of both arms
Time Frame:Up to 2-4 monthes
Safety Issue:
Description:
Measure:Specific R0/R1 resection plus radiofrequency ablation rates of both arms
Time Frame:Up to 2-4 monthes
Safety Issue:
Description:
Measure:Recurrence-free survival (RFS) of both arms
Time Frame:Up to 5 years
Safety Issue:
Description:Time to recurrence or death
Measure:5 year cancer specific survival rate of the whole population
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Progression free survival(PFS) of both arms
Time Frame:From the date of first drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 monthes
Safety Issue:
Description:
Measure:Overall survival (OS) of both arms
Time Frame:From the date of first drug administration until the date of death, assessed up to 5 years
Safety Issue:
Description:
Measure:Number of participants with surgical complications, AES and SAEs as a measure of safety
Time Frame:Each follow up visit, assessed up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yuhong Li

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