Adjuvant Systemic Chemotherapy With or Without HAI-FUDR in Patients With Resected CRLM

NCT03500874 | Terminated Phase 3 DMC

• 1 other identifier: HAI-CRCLM-ADJUVANT
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

HARVEST is an investigator-initiated prospective randomized controlled study comparing adjuvant intravenous systemic chemotherapy with or without HAI- floxuridine (FUDR) in CRC patients post-liver metastasectomy.

Conditions

Colorectal Cancer; Liver Metastases; HAI

Outcome Measures

Primary Outcomes (1)

• 3 Year Relapse Free Survival Rate

  Calculated from the time of liver metastasectomy to the time of recurrence or death, whichever came first or censored at the date of the last follow-up for recurrence-free patients that were still alive

  up to 36 months

Secondary Outcomes (3)

• Overall Survival

  up to 5 years

• Treatment-related adverse events

  Up to 36 months

• Liver-specific RFS

  Up to 36 months

Other Outcomes (1)

• Serum ctDNA methylation levels

  Up to 5 years

Study Arms (2)

HAI group

EXPERIMENTAL

Patients will receive systemic chemotherapy on days 1 and 15 using either of the following regimens: mFOLFOX6 (Oxaliplatin 85 mg/m2; Leucovorin 200mg/m2; followed by an infusion of 5-fluorouracil 2.4 g/m2 administered over 46 hours) or mFOLFIRI (Irinotecan 180mg/m2; Leucovorin 200mg/m2; followed by an infusion of 5-fluorouracil 2.4 g/m2 administered over 46 hours) For HAI, FUDR was administered as a continuous infusion of 0.12 mg/kg/day over 14 days via the HAI pump, along with dexamethasone 20 mg, and normal saline was used to fill up the 300ml pump reservoir.

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

Non-HAI group

ACTIVE COMPARATOR

Patients will receive systemic chemotherapy on days 1 and 15 using either of the following regimens: mFOLFOX6 (oxalipatin 85 mg/m2 infusion for 3 h, Leucovorin 200 mg/m2 for 3 h and 5-FU 2,400 mg/m2 continuous infusion for 46 h) or mFOLFIRI (Irinotecan 180mg/m2; Leucovorin 200mg/m2; 5-FU 2,400 mg/m2 continuous infusion for 46 h).

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

Interventions

FUDR DRUG

Floxuridine(FUDR) 0.12 mg/kg/day，on Day 1-14 through the HAI pump.

Also known as: Floxuridine

HAI group

Oxaliplatin DRUG

Oxaliplatin 180 mg/m2 IV over 90 minutes on Day 1, 15.

Also known as: Xaliplatin

HAI group; Non-HAI group

Leucovorin DRUG

Leucovorin 200mg/m2 ivd over 2 hours on Day 1

Also known as: Folinic Acid

HAI group; Non-HAI group

5FU DRUG

5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1.

Also known as: 5-Fluorouracil

HAI group; Non-HAI group

Irinotecan DRUG

Irinotecan 180mg/m2

Also known as: CPT-11

HAI group; Non-HAI group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The primary lesion has undergone or is capable of radical resection, and liver metastases can undergo R0/R1 resection (including intraoperative interventional ablation therapy), and postoperative achievement of no evidence of disease (NED).
• Histologically confirmed colorectal adenocarcinoma
• Radiologically or pathologically confirmed diagnosis of colorectal liver metastasis
• No previous surgery, interventional ablation, hepatic arterial infusion (HAI), radiotherapy, or transarterial chemoembolization (TACE) for liver metastases.
• CT, MRI, or PET/CT (if necessary) confirmed no extrahepatic metastasis.
• Normal hematologic function (platelets \> 90×10\^9/L; white blood cells \> 3×10\^9/L; neutrophils \> 1.5×10\^9/L).
• No ascites, normal coagulation function, albumin ≥ 35g/L.
• Liver function graded as Child-Pugh class A.
• Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), transaminases ≤ 5 times ULN, alkaline phosphatase ≤ 2.5 ULN.
• Serum creatinine below the upper limit of normal (ULN), or calculated creatinine clearance \> 50ml/min (using Cockcroft-Gault formula).
• ECOG performance status of 0-2
• Life expectancy ≥ 3 months
• Patients have provided a signed Informed Consent Form
• Willing and able to undergo follow-up until death or the end of the study or study termination.

You may not qualify if:

• Have had any extrahepatic metastasis after being diagnosed with colorectal cancer.
• Previous surgery, interventional ablation, hepatic arterial infusion (HAI), radiotherapy, or transarterial chemoembolization (TACE) for liver metastases.
• Liver metastases intended for interventional ablation treatment only.
• Presence of hepatic artery vascular variation identified by CTA examination, making HAI implantation unsuitable.
• Severe arterial embolism or ascites.
• Bleeding tendency or coagulation disorders.
• Hypertensive crisis or hypertensive encephalopathy.
• Severe uncontrollable systemic complications such as infection or diabetes.
• Clinically significant cardiovascular diseases such as cerebrovascular accidents (in the last 6 months before enrollment), myocardial infarction (in the last 6 months before enrollment), uncontrolled hypertension despite appropriate drug treatment, unstable angina, congestive heart failure (NYHA 2-4), and arrhythmias requiring medication.
• History of or physical examination indicating central nervous system diseases (such as primary brain tumors, uncontrollable epilepsy, any brain metastasis, or history of stroke).
• Had any other malignant tumors in the past 5 years (excluding basal cell carcinoma and/or cervical carcinoma in situ after radical surgery).
• Received any investigational drug treatment in the last 28 days before the study.
• Any residual toxicity from previous chemotherapy (excluding alopecia), such as peripheral neuropathy ≥ NCI CTC v3.0 grade 2, makes the use of a treatment regimen containing oxaliplatin not considered.
• Allergic to any drugs in the study.
• Pregnant or lactating women who are not using or refuse to use effective non-hormonal contraception (intrauterine device, barrier contraception combined with spermicidal gel, or sterilization) in women of childbearing age (last menstrual period \< 2 years ago) or fertile men who cannot or do not wish to comply with the study protocol.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• Wang DS, Pat Fong W, Wen L, Cai YY, Ren C, Wu XJ, Zhang TQ, Cao F, Zuo MX, Li BK, Zheng Y, Li LR, Chen G, Ding PR, Lu ZH, Zhang RX, Yuan YF, Pan ZZ, Li YH. Safety and efficacy of adjuvant FOLFOX/FOLFIRI with versus without hepatic arterial infusion of floxuridine in patients following colorectal cancer liver metastasectomy (HARVEST trial): A randomized controlled trial. Eur J Cancer. 2025 Jan;214:115154. doi: 10.1016/j.ejca.2024.115154. Epub 2024 Nov 30.

  PMID: 39644535 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Floxuridine; Oxaliplatin; Leucovorin; Fluorouracil; Irinotecan

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)

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

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: Professor

Study Record Dates

• First Submitted: April 8, 2018
• First Posted: April 18, 2018
• Study Start: May 28, 2018
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: January 22, 2024

Record last verified: 2024-01

Locations

CN (1)