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

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ClinicalTrials.gov Identifier: NCT02102789
Recruitment Status : Recruiting
First Posted : April 3, 2014
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
Yuhong Li, Sun Yat-sen University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: mFOLFOX6 Drug: HAI Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 142 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : March 2014
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Floxuridine

Arm Intervention/treatment
Experimental: Systemic chemotherapy
Patients 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.
Drug: mFOLFOX6
Patients 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.
Other Names:
  • Oxaliplatin
  • Leucovorin
  • 5-fluorouracil

Experimental: Systemic chemotherapy combined with HAI

Patients 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.

Drug: mFOLFOX6
Patients 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.
Other Names:
  • Oxaliplatin
  • Leucovorin
  • 5-fluorouracil

Drug: HAI

Patients will receive HAI every 28 days: 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 administration will be a 14-day continuous infusion using the HAI pump.

Other Names:
  • floxuridine (FUDR)
  • dexamethasone




Primary Outcome Measures :
  1. Complete resection rates (R0 resection rates) (defined as no macroscopic or microscopic residual tumor) of both arms [ Time Frame: Up to 2-4 months ]

Secondary Outcome Measures :
  1. Overall response rates (ORR) of both arms [ Time Frame: Up to 4-8 monthes ]
  2. R1 resection rates (with microscopic residual tumor) of both arms [ Time Frame: Up to 2-4 monthes ]
  3. Specific R0/R1 resection plus radiofrequency ablation rates of both arms [ Time Frame: Up to 2-4 monthes ]
  4. Recurrence-free survival (RFS) of both arms [ Time Frame: Up to 5 years ]
    Time to recurrence or death

  5. 5 year cancer specific survival rate of the whole population [ Time Frame: Up to 5 years ]
  6. 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 ]
  7. 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 ]
  8. 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 ]


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT02102789


Contacts
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Contact: Yu-hong Li, MD, Ph D liyh@sysucc.org.cn

Locations
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China, Guangdong
Sun Yat-sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Yu-hong Li, MD, Ph D       liyh@sysucc.org.cn   
Principal Investigator: Yu-hong Li, MD, Ph D         
Sponsors and Collaborators
Yuhong Li
Investigators
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Principal Investigator: Yu-hong Li, MD, Ph D Sun Yat-sen University
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Responsible Party: Yuhong Li, MD, Ph D, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT02102789    
Other Study ID Numbers: Frozen-2
First Posted: April 3, 2014    Key Record Dates
Last Update Posted: October 29, 2019
Last Verified: October 2019
Additional relevant MeSH terms:
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Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Leucovorin
Dexamethasone
Fluorouracil
Oxaliplatin
Floxuridine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents