Clinical trial NCT05349331: Watch and Wait Versus Surgical Treatment for Clinical Complete Responders After Non-Curative Therapy for Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hepatocellular Carcinoma
Keywords: Conversion Reaction
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2022-04-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 24 months
Secondary outcomes:
measure: Time to treatment failure
timeFrame: 24 months
measure: Overall survival
timeFrame: 24 months
measure: pCR rate in surgery group
timeFrame: 24 months
Other outcomes:
measure: Correlation of serum tumor molecular marker with survival
timeFrame: 24 months
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
Study officials:
References: