A Trial of Adjuvant Therapy After Hepatocarcinoma Resection Based on Folate Receptor-positive Circulating Tumor Cells

• ClinicalTrials.gov Identifier: NCT04521491
• Recruitment Status: Not yet recruiting
• First Posted: August 20, 2020
• Last Update Posted: August 20, 2020
• Sponsor: Eastern Hepatobiliary Surgery Hospital
• Information provided by (Responsible Party): Shen Feng, Eastern Hepatobiliary Surgery Hospital

Study Description

Brief Summary:

The aim of this study is to analyze the therapeutic effect of postoperative adjuvant chemotherapy with FOLFOX4 after hepatocarcinoma resection based on folate receptor-positive circulating tumor cells. Patients receiving curative resection (R0) were randomized to postoperative FOLFOX4 group and no FOLFOX4 group. The time to recurrence, the overall survival as well as the incidence of complications after therapy was observed to confirm the role of postoperative adjuvant therapy of FOLFOX4.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Drug: FOLFOX4(infusional fluorouracil [FU], leucovorin [LV], and oxaliplatin [OXA]).	Not Applicable

Detailed Description:

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death globally. Hepatectomy remains the most widely practiced radical treatment for HCC despite having a high associated recurrence rate, approximately 70% at 5 years after surgery, which often hampers further improvement in survival for these patients. And until now although a lot of different adjuvant therapies had been tried in the clinic, but their role in preventing recurrence remain controversial. As a research of a phase Ⅲ randomize study showed that FOLFOX4 (infusional fluorouracil [FU], leucovorin[LV], and OXA) served as palliative chemotherapy can induce higher overall survival, progression-free survival and response rate comparing to doxorubicin in patients with advanced hepatocellular carcinoma from Asia. The safety data was also acceptable. The chemotherapy of FOLFOX has been accepted by many guidelines and recommended for systematic treatment of advanced HCC. However, the effect of this systemic chemotherapy for recurrent HCC after partial hepatectomy remains to be investigated.

Circulating tumor cells (CTC) have played an important role in early diagnosis of tumors, monitoring of recurrence and metastasis, judgment of patient prognosis, and guidance of postoperative adjuvant treatment. CTC counts can be used to assist diagnosis and evaluation of postoperative prognosis. Previous studies have also shown that folate receptors (FR) are highly expressed in HCC. The detection of circulating tumor cells based on folate receptor (FR+CTC) has been proved to be a sensitive and effective method for detecting CTC.

Patients with HCC who received curative liver resection and with the preoperative FR+CTC level higher than 18.4FU/3mL were randomly assigned 1:1 by the doctors to receive placebo(control group) or FOLFOX4 (treatment group). All patients in the treatment group received FOLFOX4 at most 12 cycles beginning from the 4th week after liver resection. The outcomes of patients were evaluated during the 3-years follow up.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 184 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Study on the Effect of Postoperative Adjuvant Chemotherapy With FOLFOX4 After Hepatocarcinoma Resection Based on Folate Receptor-positive Circulating Tumor Cells
• Estimated Study Start Date: December 1, 2020
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: FOLFOX4; Patients who will receive FOLFOX4 chemotherapy after liver resection	Drug: FOLFOX4(infusional fluorouracil [FU], leucovorin [LV], and oxaliplatin [OXA]).; FOLFOX4 (OXA 85 mg/m2 intravenously [IV] on day 1; LV 200 mg/m2 IV from hour 0 to 2 on days 1 and 2; and FU 400 mg/m2 IV bolus at hour 2, then 600 mg/m2 over 22 hours on days 1 and 2, once every 2 weeks.All patients in the treatment group will receive FOLFOX4 at most 12 times beginning from the 4th week after liver resection.
No Intervention: placebo; No adjuvant therapy after liver resection

Outcome Measures

Primary Outcome Measures :

1. Recurrence free survival(RFS) [ Time Frame: Up to 2 years ]
   the time from randomization to documented progression

Secondary Outcome Measures :

1. Time to recurrence (TTR) [ Time Frame: Up to 2 years ]
   the time from randomization to documented progression
2. Overall survival(OS) [ Time Frame: Up to 2 years ]
   the time from randomization to documented progression

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients with HCC who received curative liver resection (R0);
2. Karnofsky Performance Score performance over 60;
3. The functions of the kidney, heart and lung and the blood system are normal and fittable for Licardin therapy;
4. The liver function is of grade A or B in Child-Pugh classification;
5. Patients agreed to collect peripheral blood for detection of CTC at the designated time point;
6. Patients should sign the informed consent of this study.

Exclusion Criteria:

1. If postoperative liver function is Child C, it cannot tolerate chemotherapy;
2. Blood transfusion history within 1 month before enrollment;
3. Severe gastroesophagealvarices with red sign or with variceal hemorrhage before;
4. Malignant or metastatic tumor in other sites in last 5 years;
5. Patients can not be followed-up regularly;
6. Patients participating in other trials or received other treatment previously.

Contacts and Locations

Locations

China, Shanghai

Eastern hepatobilliary surgery hospital

Shanghai, Shanghai, China, 200438

Sponsors and Collaborators

Eastern Hepatobiliary Surgery Hospital

More Information

• Responsible Party: Shen Feng, MD, Eastern Hepatobiliary Surgery Hospital
• ClinicalTrials.gov Identifier: NCT04521491
• Other Study ID Numbers: EHBHKY2020-01-003
• First Posted: August 20, 2020
• Last Update Posted: August 20, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shen Feng, Eastern Hepatobiliary Surgery Hospital:

hepatocellular carcinoma; adjuvant therapy; FOLFOX4; circulating tumor cells; folate receptor

Additional relevant MeSH terms:

Carcinoma, Hepatocellular; Neoplastic Cells, Circulating; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Leucovorin; Fluorouracil; Oxaliplatin; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antidotes; Protective Agents; Vitamin B Complex; Vitamins; Micronutrients