Clinical trial NCT06389422: Phase II Study of Moderate-dose Hypofractionated RT Combined With Pembrolizumab for HCC With Diffuse Tumor Thrombosis
Official title: Phase II Study of Moderate-dose Hypofractionated Radiotherapy Combined With Pembrolizumab for Hepatocellular Carcinoma With Diffuse Tumor Thrombosis Involved Both Left and Right Liver
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Radiotherapy
Pembrolizumab
Tumor Thrombosis
Keywords: Hepatocellular Carcinoma
Radiotherapy
Pembrolizumab
Tumor Thrombosis
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2024-04-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-center, single-arm, open-label study that includes patients meeting the inclusion criteria (liver-GTV volume \< 700ml or estimated liver-GTV V5 \< 300ml) with hepatocellular carcinoma with diffuse tumor thrombosis involving both left and right lobes. All lesions receive moderate-dose hypofractionated intensity-modulated radiotherapy, with a gross tumor dose of 25Gy/5f, and a maximum dose of 35Gy/5f at the tumor center. One week before or during the radiotherapy, patients receive concurrent Pembrolizumab at a dose of 200mg. Subsequently, Pembrolizumab is administered intravenously every 3 weeks. Follow-up examinations are conducted 1-3 months post-radiotherapy. Lenvatinib 4mg may be used for maintenance therapy with Pembrolizumab if there are no contraindications. Maintenance therapy is continued until disease progression or intolerance. The primary endpoint is median overall survival (mOS), and secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and toxicity.


Eligibility criteria: Inclusion Criteria:

1. Confirmed clinically or histopathologically as hepatocellular carcinoma, concurrently with portal vein thrombosis or hepatic vein thrombosis;
2. Age 18-90 years;
3. Liver-GTV volume\<700ml or the estimated volume of Liver-GTV receiving less than 5 Gy of irradiation\<300ml but the average dose of Liver-GTV needs to be \<18Gy;
4. Allowed previous treatment including TACE, RFA, surgery, chemotherapy, targeted therapy, etc., but not including ICIs such as anti-PD-1, anti-PD-L1, or anti-PD-L2 therapies;
5. ECOG performance status 0-2, expected survival greater than 1 month;
6. Allowing patients with distant metastases;
7. Child-Pugh A5, A6, B7 and B8;
8. ALT within 2.5 times the normal upper limit; AST within 2.5 times the normal upper limit; TBIL \<60umol/L.
9. No significant abnormalities in the electrocardiogram, no apparent heart failure, and no contraindications for anti-PD-1 treatment;
10. CRE, BUN within 2.5 times the normal upper limit;
11. Hb ≥ 50g/L, ANC ≥ 0.5 × 10\^9 /L, PLT ≥ 30 × 10\^9 /L; patients with a history of gastrointestinal bleeding must be controlled for more than 2 weeks before enrollment with Hb ≥ 60g/L and a significant rising trend;
12. Patients voluntarily participate in this clinical trial and sign an informed consent form.

Exclusion Criteria:

1. Currently participating in other clinical trials;
2. Previously received abdominal radiotherapy or liver transplantation;
3. Individuals with severe chronic disease conditions affecting vital organs such as the heart, kidneys, or liver;
4. Severe ascites with noticeable symptoms, anticipated to be unrelieved after treatment.
5. Suspected or confirmed drug addiction, medicine abuse,or alcoholism
6. Pregnant or lactating women;
7. Severe mental or neurological disorders
8. Presence of other life-threatening malignancy within the last 3 years before the start of the study (excluding superficial skin cancer, localized low-grade malignant tumor and in situ carcinoma).

Primary outcomes:
measure: Median Overall Survival
timeFrame: 24 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Assessment in 1 to 3 months after radiotherapy
measure: Progression-free Survival
timeFrame: 24 months
measure: Toxicity
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciecnces and Peking Union Medical College
state: Beijing
Study officials:
References: