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

NCT02102789 | Recruiting Phase 3 DMC

• 1 other identifier: Frozen-2
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Complete resection rates (R0 resection rates) (defined as no macroscopic or microscopic residual tumor) of both arms

  Up to 2-4 months

Secondary Outcomes (8)

• Overall response rates (ORR) of both arms

  Up to 4-8 monthes

• R1 resection rates (with microscopic residual tumor) of both arms

  Up to 2-4 monthes

• Specific R0/R1 resection plus radiofrequency ablation rates of both arms

  Up to 2-4 monthes

• Recurrence-free survival (RFS) of both arms

  Up to 5 years

• 5 year cancer specific survival rate of the whole population

  Up to 5 years

Study Arms (2)

Systemic chemotherapy

EXPERIMENTAL

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

Systemic chemotherapy combined with HAI

EXPERIMENTAL

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; Drug: HAI

Interventions

mFOLFOX6 DRUG

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.

Also known as: Oxaliplatin, Leucovorin, 5-fluorouracil

Systemic chemotherapy; Systemic chemotherapy combined with HAI

HAI DRUG

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.

Also known as: floxuridine (FUDR), dexamethasone

Systemic chemotherapy combined with HAI

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yuhong Li: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Leucovorin; Fluorouracil; Floxuridine; Dexamethasone

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Yu-hong Li, MD, Ph D

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yu-hong Li, MD, Ph D

CONTACT

liyh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Ph D

Study Record Dates

• First Submitted: March 31, 2014
• First Posted: April 3, 2014
• Study Start: March 1, 2014
• Primary Completion: August 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 4, 2024

Record last verified: 2024-03

Locations

CN (1)