Watch and Wait Versus Surgical Treatment for Clinical Complete Responders After Non-Curative Therapy for Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

— WATCH  

Official title:

Watch and Wait Versus Surgical Treatment for Clinical Complete Responders After Non-Curative Therapy for Hepatocellular Carcinoma: A Phase II Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05349331
• Other study ID #: B2022-119-X01
• Status: Recruiting
• Phase: N/A
• Start date: May 5, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2023
• Source: Sun Yat-sen University
• Contact: Wei He
• Phone: 15521248313
• Email: hewei[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hepatocellular carcinoma (HCC) accounts for more than 90% of primary liver cancers and is the sixth most common cancer in the world and ranked third in mortality. Most patients with HCC are diagnosed at an advanced stage and miss the opportunity for radical surgical resection, therefore, most patients receive mainly non-curative local and systemic treatments.

Anti-angiogenic drugs with immunotherapy for unresectable HCC has achieved an objective response rate of about 30%. In addition, transarterial hepatic artery chemoembolization and hepatic artery infusion chemotherapy have further increased the objective response rate and depth of tumor regression. For patients with initially unresectable HCC, conversion therapy can result tumor shrinkage and downstaging, ultimately allowing patients the opportunity to undergo resection. However, it raise the question of whether surgical resection of the tumor is still necessary after achieving clinical complete response? On the one hand, some researchers believe that as long as resection is feasible, the tumor must be completely removed. Viable tumor cells may still remain and become a source of tumor recurrence. On the other hand, some researchers believe that patients who achieve clinical complete response after conversion therapy can consider a non-surgical watch and wait strategy. Whether the inactive lesions with clinical complete response still require surgical resection is still inconclusive. This study compared the efficacy and safety of surgical resection versus non-surgical resection in the treatment of hepatocellular carcinoma patients who achieved clinical complete response after hepatic arterial intervention (chemoembolization/infusion chemotherapy) combined with targeted and immunosuppressive therapy. It is expected to provide reliable clinical evidence support for guiding the treatment of such patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years old.

• Patients with clinical diagnosis of hepatocellular carcinoma without extrahepatic metastasis, and two liver surgeons evaluated as unresectable.

• AFP=400ug/L or PIVKA-II=1000mAU/mL before initial treatment.

• Initial treatment is hepatic arterial intervention (chemoembolization/infusion chemotherapy), combined targeted therapy (sorafenib, lenvatinib, donafenib, apatinib, bevacizumab) and immune checkpoint inhibitor therapy (PD-1\PD-L1).

• After transarterial infusion chemotherapy combined with targeted and immunotherapy treatment, the tumor evaluation is clinical complete response, that is, the following two criteria are met: 1. Two consecutive imaging assessments (one month apart) tumor complete response (CR, mRECIST) standard) 2. Two consecutive tumor markers (one month apart) AFP and PIVKA-II = the upper limit of the normal value

• The patients with clinical complete response were evaluated by two liver surgeons as resectable.

• Normal hematological function (platelets>75×109/L; leukocytes>3.0×109/L; neutrophils>1.5×109/L)

• Serum bilirubin = 1.5 times the upper limit of normal (ULN), transaminases = 3 times ULN

• No ascites, normal coagulation function, albumin=30g/L

• Child-Pugh class A

• Serum creatinine less than 1.5 times the upper limit of normal (ULN)

• ECOG score 0-1

• Life expectancy > 3 months

Exclusion Criteria:

• Received other tumor treatments other than hepatic artery interventional therapy, targeted and immunotherapy

• Any of the following conditions within the first 12 months of the study: myocardial infarction, severe/unstable angina, coronary artery bypass grafting, congestive heart failure, cerebrovascular accident (including transient ischemic attack), Pulmonary embolism; ongoing: arrhythmia of grade =2 by NCI-CTCAE criteria, QTc prolongation (>450 ms in men, >470 ms in women);

• Renal insufficiency requires peritoneal dialysis or hemodialysis;

• Serious dysfunction of other important organs;

• A second primary malignant tumor was diagnosed in the past;

• Known or new evidence of brain or leptomeningeal lesions; Hemophilia or bleeding tendency, taking anticoagulation therapy such as coumarin derivatives in therapeutic doses;

• Pregnant or lactating women, all female patients of childbearing potential must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative;

• History of previous organ transplantation;

• Known HIV infection;

• Allergy to chemotherapy drugs;

• Patients with other serious acute or chronic physical or psychiatric diseases or abnormal laboratory tests that may increase the risk associated with participating in the study, or may interfere with the interpretation of the study results or the investigators consider unsuitable for enrollment.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Procedure:
• Liver Resection
Surgical resection treatment: laparoscopic or open liver resection is performed, and targeted and immunotherapy are not continued after surgery.

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	Correlation of serum tumor molecular marker with survival	Correlation of serum tumor molecular marker methylation level with pCR in surgery group and tumor progression in non-surgery group.	24 months
Primary	Progression-free survival	assessed using mRECIST criteria, defined as the survival rate of patients without tumor progression from randomization to the end.	24 months
Secondary	Time to treatment failure	Defined as the time from randomization to the first documented treatment failure (ie, local recurrence or progression or death from any cause).	24 months
Secondary	Overall survival	defined as the time from randomization to death from any cause.	24 months
Secondary	pCR rate in surgery group	Pathological complete response (pCR) was defined as the absence of residual viable tumor cells on hematoxylin and eosin staining on completely resected tumor specimen sections.	24 months