FUDR/Oxaliplatin HAI Plus Irinotecan vs. FOLFOXIRI Chemotherapy in Treating Initially Unresectable CRCLM

NCT03678428 | Terminated Phase 3

• 1 other identifier: TRIUMPH
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the trial is to compare the objective response rates of FUDR/Oxaliplatin HAI plus CPT-11 and FOLFOXIRI chemotherapy in patients with initially non-resectable metastatic colorectal cancer liver metastases. The patients will be treated with systemic FOLFOXIRI chemotherapy or FUDR/Oxaliplatin hepatic arterial infusion with CPT-11 systemic chemotherapy.

Conditions

Metastatic Colorectal Cancer; Liver Metastases

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate and bilateral 95% confidence interval

  defined as complete remission rates and partial remission rates after treatment.

  Up to 2-4 months

Secondary Outcomes (6)

• R0 resection rates

  Up to 2-4 months

• Depth of tumor regression(DpR)

  Up to 2-4 months

• Progress-free Survival(PFS)

  Up to 2-4 months

• Relapse-free Survival(RFS) of patients with resectable tumor

  Up to 2-4 months

• Overall Survival(OS)

  Up to 2-4 months

Study Arms (2)

FUDR/Oxaliplatin HAI plus irinotecan

EXPERIMENTAL

Patients will receive Systemic CPT-11 + HAI (FUDR+L-OHP) every 28 days: Irinotecan 150 mg/m2 IV over 90 minutes on Day 1; followed by Oxaliplatin 85 mg/m2 over 3 hours through the HAI pump on Day 1 and 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. then Irinotecan 150 mg/m2 IV over 90 minutes on Day 15, followed by Oxaliplatin 85 mg/m2 IV over 3 hours on Day 15. 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: Irinotecan; Drug: Oxaliplatin HAI; Drug: Floxuridine

FOLFOXIRI

ACTIVE COMPARATOR

Patients will receive Systemic FOLFOXIRI every 28 days: Irinotecan 150 mg/m2 IV over 90 minutes on Day 1 and Day 15; Oxaliplatin 85 mg/m2 IV in 3-6 hours on Day 1 and Day 15; Leucovorin 200mg/m2 and 5-FU 2400mg/m2 CIV in 46 hours on Day 1 and Day 15.

Drug: Irinotecan; Drug: Leucovorin; Drug: 5-FU; Drug: Oxaliplatin

Interventions

Irinotecan DRUG

Irinotecan 150 mg/m2 IV over 90 minutes on Day 1 and 15.

FOLFOXIRI; FUDR/Oxaliplatin HAI plus irinotecan

Oxaliplatin HAI DRUG

Oxaliplatin 85 mg/m2 over 3 hours will be administered through the HAI pump on day 1. Oxaliplatin 85 mg/m2 IV over 3 hours on day 15.

FUDR/Oxaliplatin HAI plus irinotecan

Floxuridine DRUG

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.

FUDR/Oxaliplatin HAI plus irinotecan

Leucovorin DRUG

Leucovorin 200mg/m2 IV on Day 1 and 15.

FOLFOXIRI

5-FU DRUG

5-FU 2400mg/m2 CIV in 46h on Day 1 and 15.

FOLFOXIRI

Oxaliplatin DRUG

Oxaliplatin 85 mg/m2 IV over 3 hours on Day1 and 15.

FOLFOXIRI

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 and ≤70.
• Diagnosed as colorectal adenocarcinoma by histology.
• Confirmed as liver metastases by medical imaging or pathology.
• MDT determined as unresectable liver metastases, defined as:①more than 5 metastases; ②unable to conduct R0 resection; ③no sufficient residual liver volume after resection; ④none of 3 hepatic vein can be reserved after resection, no sufficient blood supply or bibliary duct can be reserved, none of 2 adjacent liver segment can be reserved. Whenever meets any of the criteria mentioned above would be defined as unresectable liver metastases.
• No previous treatment aiming at treating liver metastases, including chemotherapy, surgery, radiotherapy, transcatheter hepatic arterial chemoembolization(TACE) or target therapy.
• Confirmed by CT, MRI or PET/CT(if necessary) that there is no extrahepatic metastases or only oligos extrahepatic metastases(no more than 2 organs and 5 leisions, maximum diameters of single leision ≤ 1cm).
• Unsuitable for cetuximab treatment(RAS mutation, unable to afford the cost).
• No hematologic dysfunction(Platelets \>90×10\^9/L; WBC \>3×10\^9/L; Neutrophil \>1.5×109/L).
• Serum bilirubin ≤ 1.5 × ULN; aminotransferase ≤ 5 × ULN.
• No ascites; no coagulation dysfunction; albumin ≥ 30g/L.
• Hepatic function was classified as class A by Child-Pugh classification.
• Serum creatinine \< 1 × ULN, or creatinine clearance rate(CCR) \> 50ml/min(calculated by Cockcroft-Gault formula).
• ECOG scored as 0-1.
• Life expectancy \> 3 months.
• Informed consent.

You may not qualify if:

• Presence of extensive extrahepatic metastases(more than 2 organs and 5 leisions, or maximum diameter of single leision \> 10 cm).
• Severe arterial embolism or ascites.
• Presence of hemorrhagic tendency or coagulation dysfunction.
• Presentive of hypertensive crisis or hypertensive encephalopathy.
• Severe uncontrolled systemic complications, such as infection or diabetes.
• Severe clinical CVD(cardiovascular disease), such as cerebrovascular accident(within 6 months before recruitment), myocardial infarction(within 6 months before recruitment), uncontrolled hypertension; unstable angina pectoris; congestive heart-failure(NYHA 2-4 grade); arrhythmia that needs medication treatment.
• Previous diagnosed or physical examination showed presence of central nervous system(CNS) disease(i.e. primary brain tumor, epilepsy uncontrolled by standard treatment, any history of brain metastases or stroke).
• Previous history of other malignancy within 5 years(except basal cell carcinoma after radical resection and/or cervical carcinoma in situ).
• Received any medication under research within 28 days before the trial.
• Any residual toxicity of previous chemotherapy(except hair loss), i.e. peripheral neuropathy ≥ NCI CTC v3.0 Grade 2, will be excluded from oxaliplatin-based chemotherapy regimen research pair.
• Allergic to any medication involved in the trial.
• Pregnant and 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

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; Floxuridine; Leucovorin; Fluorouracil; Oxaliplatin

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)

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

Study Officials

• Yuhong Li, MD

  Sun Yat-sen University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Medical Oncology, Principal Investigator, Clinical Professor, Yuhong Li

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 19, 2018
• Study Start: December 31, 2021
• Primary Completion: October 31, 2022
• Study Completion: December 31, 2022
• Last Updated: February 16, 2023

Record last verified: 2023-02

Locations

CN (1)