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

Colorectal Cancer Clinical Trial

Official title:

Adjuvant Systemic Chemotherapy With or Without Hepatic Arterial Infusion Using Floxuridine in Patients Following Colorectal Cancer Liver Metastases Resection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03500874
• Other study ID #: HAI-CRCLM-ADJUVANT
• Status: Terminated
• Phase: Phase 3
• Start date: May 28, 2018
• Est. completion date: August 31, 2021

Study information

• Verified date: January 2024
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 92
• Est. completion date: August 31, 2021
• Est. primary completion date: August 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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:

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• HAI
• Liver Metastases
• Neoplasm Metastasis

Intervention

Drug:
• FUDR
Floxuridine(FUDR) 0.12 mg/kg/day,on Day 1-14 through the HAI pump.
• Oxaliplatin
Oxaliplatin 180 mg/m2 IV over 90 minutes on Day 1, 15.
• Leucovorin
Leucovorin 200mg/m2 ivd over 2 hours on Day 1
• 5FU
5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1.
• Irinotecan
Irinotecan 180mg/m2

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Up to 5 years
Primary	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	Overall Survival	From date of randomization until the date of death from any cause, assessed up to 5 years	up to 5 years
Secondary	Treatment-related adverse events	Number of patients with adverse events and severity measured according to the NCI CTC 3.0 criteria	Up to 36 months
Secondary	Liver-specific RFS	Measure of the time period during which a patient remains free from the recurrence of liver-related events	Up to 36 months