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TerminatedNCT03500874Updated Jan 22, 2024

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

A Phase 3 interventional study of FUDR and Oxaliplatin in Colorectal Cancer, Liver Metastases and HAI, sponsored by Sun Yat-sen University. Terminated at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-01-22.

Sponsored by Sun Yat-sen University · Phase 3, Interventional, and Treatment

Why this study was terminated
The study was terminated prematurely due to FUDR production halt in China
Phase
Phase 3
Study type
Interventional
Enrollment
92
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

Read the detailed description

Numerous retrospective studies have indicated a positive synergistic effect of combining adjuvant oxaliplatin/irinotecan-based doublet systemic chemotherapy and hepatic arterial infusion (HAI) for colorectal cancer (CRC) patients following colorectal cancer liver metastases (CRLM) resection. However, this strategy has not been evaluated prospectively to date. 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.

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Conditions studied

  • Colorectal Cancer
  • Liver Metastases
  • HAI
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In context

Colorectal Neoplasms

5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.

This study's enrollment of 92 is above the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.

Browse Colorectal Neoplasms studies →

Lead sponsor

Sun Yat-sen University is the lead sponsor of 1,644 studies on the registry; 602 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. 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).
  2. Histologically confirmed colorectal adenocarcinoma
  3. Radiologically or pathologically confirmed diagnosis of colorectal liver metastasis
  4. No previous surgery, interventional ablation, hepatic arterial infusion (HAI), radiotherapy, or transarterial chemoembolization (TACE) for liver metastases.
  5. CT, MRI, or PET/CT (if necessary) confirmed no extrahepatic metastasis.
  6. Normal hematologic function (platelets > 90×10\^9/L; white blood cells > 3×10\^9/L; neutrophils > 1.5×10\^9/L).
  7. No ascites, normal coagulation function, albumin ≥ 35g/L.
  8. Liver function graded as Child-Pugh class A.
  9. Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), transaminases ≤ 5 times ULN, alkaline phosphatase ≤ 2.5 ULN.
  10. Serum creatinine below the upper limit of normal (ULN), or calculated creatinine clearance > 50ml/min (using Cockcroft-Gault formula).
  11. ECOG performance status of 0-2
  12. Life expectancy ≥ 3 months
  13. Patients have provided a signed Informed Consent Form
  14. Willing and able to undergo follow-up until death or the end of the study or study termination.

Exclusion criteria

Exclusion Criteria:

  1. Have had any extrahepatic metastasis after being diagnosed with colorectal cancer.
  2. Previous surgery, interventional ablation, hepatic arterial infusion (HAI), radiotherapy, or transarterial chemoembolization (TACE) for liver metastases.
  3. Liver metastases intended for interventional ablation treatment only.
  4. Presence of hepatic artery vascular variation identified by CTA examination, making HAI implantation unsuitable.
  5. Severe arterial embolism or ascites.
  6. Bleeding tendency or coagulation disorders.
  7. Hypertensive crisis or hypertensive encephalopathy.
  8. Severe uncontrollable systemic complications such as infection or diabetes.
  9. 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.
  10. History of or physical examination indicating central nervous system diseases (such as primary brain tumors, uncontrollable epilepsy, any brain metastasis, or history of stroke).
  11. Had any other malignant tumors in the past 5 years (excluding basal cell carcinoma and/or cervical carcinoma in situ after radical surgery).
  12. Received any investigational drug treatment in the last 28 days before the study.
  13. 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.
  14. Allergic to any drugs in the study.
  15. 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.
  16. Presence of any other diseases, functional impairment due to metastatic lesions, or suspicious findings in the physical examination suggesting contraindications to the use of the investigational drug or placing the patient at a high risk of treatment-related complications.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
92 participants (actual)

Study arms

  • Experimental
    HAI group

    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

  • Active comparator
    Non-HAI group

    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

  • DrugFUDR

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

    Also known as: Floxuridine

  • DrugOxaliplatin

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

    Also known as: Xaliplatin

  • DrugLeucovorin

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

    Also known as: Folinic Acid

  • Drug5FU

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

    Also known as: 5-Fluorouracil

  • DrugIrinotecan

    Irinotecan 180mg/m2

    Also known as: CPT-11

06

What researchers measure

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

    Time frame: up to 36 months

Secondary outcomes

  1. Overall Survival

    From date of randomization until the date of death from any cause, assessed up to 5 years

    Time frame: up to 5 years

  2. Treatment-related adverse events

    Number of patients with adverse events and severity measured according to the NCI CTC 3.0 criteria

    Time frame: Up to 36 months

  3. Liver-specific RFS

    Measure of the time period during which a patient remains free from the recurrence of liver-related events

    Time frame: Up to 36 months

Other outcomes

  1. Serum ctDNA methylation levels

    The methylation status of blood ctDNA at a specific time point (e.g., postoperatively) was considered positive if either of the two markers (SEPT9 and NPY) yielded results above zero. Conversely, it was deemed negative if both markers showed an absence of methylation.

    Time frame: Up to 5 years

07

Study locations

1 site
  • Sun Yat-sen University Cancer Center
    Guangzhou, Guangdong 510060, China
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References and documents

Individual participant data

Plan to share: Undecided — Study Protocol

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 22, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03500874
Lead sponsor
Sun Yat-sen University
Responsible party
Yuhong Li (Professor, Sun Yat-sen University) — Principal investigator
First posted
Apr 18, 2018
Start date
May 28, 2018
Primary completion
Aug 31, 2021
Completion
Aug 31, 2021
Last update
Jan 22, 2024

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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