Clinical trial NCT02102789: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2014-04-03
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Complete resection rates (R0 resection rates) (defined as no macroscopic or microscopic residual tumor) of both arms
timeFrame: Up to 2-4 months
Secondary outcomes:
measure: Overall response rates (ORR) of both arms
timeFrame: Up to 4-8 monthes
measure: R1 resection rates (with microscopic residual tumor) of both arms
timeFrame: Up to 2-4 monthes
measure: Specific R0/R1 resection plus radiofrequency ablation rates of both arms
timeFrame: Up to 2-4 monthes
measure: Recurrence-free survival (RFS) of both arms
timeFrame: Up to 5 years
measure: 5 year cancer specific survival rate of the whole population
timeFrame: Up to 5 years
measure: Progression free survival(PFS) of both arms
timeFrame: 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
measure: Overall survival (OS) of both arms
timeFrame: From the date of first drug administration until the date of death, assessed up to 5 years
measure: Number of participants with surgical complications, AES and SAEs as a measure of safety
timeFrame: Each follow up visit, assessed up to 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yu-hong Li, MD, Ph D
role: PRINCIPAL_INVESTIGATOR
References: