Clinical trial NCT06870942: Efficacy and Safety of Radiotherapy in Oligoprogressive HCC Following First-line PD-1 Therapy
Official title: Efficacy and Safety of Radiotherapy in Oligoprogressive HCC Following First-line PD-1 Therapy: A Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HCC - Hepatocellular Carcinoma
Radiotherapy
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2025-03-11
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Immune checkpoint inhibitors (ICIs) have significantly improved the survival outcomes of HCC patients. However, a considerable proportion of patients eventually experience disease progression due to the development of resistance. Among these, oligoprogression is a common manifestation, occurring in 10-55.3% of advanced cancer patients. Local therapy, especially radiotherapy (RT), has been increasingly considered in the setting of oligoprogression to overcome ICIs resistance and delay the need to change systemic therapy. Therefore, this study aimed to explore the efficacy and safety of RT in oligoprogressive HCC following first-line PD-1 therapy.


Eligibility criteria: Inclusion Criteria:

1. Diagnosis of hepatocellular carcinoma (HCC) based on either histopathologic or cytologic findings or a diagnosis of cirrhosis and HCC with classical imaging characteristics;
2. HCC patients with oligoprogression after first-line PD-1 therapy ;
3. Stable Disease for at least 3 months after first-line PD-1 therapy ;
4. Oligoprogressive disease in 5 or fewer lesions and 3 or fewer organs
5. Tumor staged as BCLC stage C
6. ECOG performance status: 0-1.
7. Life expectancy \>=6 months.
8. No history of irradiation.
9. aged 18 to 75 years old are eligible.
10. Patients must be able to understand and willing to sign a written informed consent document.
11. Female patients within childbearing age or male patients whose sexual partners are women within childbearing age need to take effective contraceptive measures throughout the treatment period and 6 months after the treatment.

Exclusion Criteria:

1. Fibrous lamina hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma;
2. History of hepatic encephalopathy or liver transplantation;
3. Pleural effusion, ascites and pericardial effusion with clinical symptoms or needing drainage. Only a small amount of pleural effusion, ascites and pericardial effusion without symptoms could be included;
4. Untreated hepatitis infection: HBV DNA\>2000IU/mlor104 copy/ml, HCV RNA\> 103copy/ml, both HbsAg and anti-HCV body are positive;
5. Evidence with active central nervous system (CNS) metastases. Patients can be included if the CNS metastasis can be treated and the neurological symptoms can be restored to a level of \<=1 degree of CTCAE (except for residual signs or symptoms associated with CNS treatment) for at least 2 weeks before the enrollment. In addition, patients must have not be treated with a corticosteroid, or just be treated with a stable dose of \<= 10 mg prednisone/day (or equivalent dose) or with a dose reduced to 10 mg prednisone/day;
6. In the past six months, there was a history of gastrointestinal perforation and/or fistula, intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), inflammatory bowel disease or extensive intestinal resection (partial or extensive intestinal resection with chronic diarrhea), Crohn's disease, ulcerative colitis or chronic diarrhea;
7. History of symptomatic interstitial lung disease or other conditions that may cause confusion when discovering or managing suspicious drug-related lung toxicity;
8. Evidence of active pulmonary tuberculosis (TB). Patients diagnosed with active tuberculosis infection within 1 year should be excluded even if they have been treated;
9. Positive test of immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS);
10. Severe infections are in active stage or under clinical control. Severe infections occurred within 4 weeks before the first treatment, including but not limited to hospitalization due to infection, bacteremia or complications of severe pneumonia;
11. Patients with active, known or suspected autoimmune diseases. Patients with the following conditions can be selected: vitiligo, type I diabetes, residual thyroid dysfunction caused by autoimmune thyroiditis that just need hormone replacement therapy, or diseases that will not relapse without external stimulating factors;
12. Inoculation of any anti-infective vaccine (such as influenza vaccine, varicella vaccine, etc.) within past 4 weeks;
13. Large surgical (craniotomy, thoracotomy or laparotomy) or unhealed wounds, ulcers or fractures have been performed in the past four weeks;
14. Uncontrolled metabolic disorders or other non-malignant organ or systemic diseases or secondary tumors may lead to higher medical risks and/or uncertainty in survival assessment;
15. Some acute or chronic diseases, psychiatric disorders or abnormal laboratory test values that may lead to the result: increased risk of participating in the study or drug administration, or interfering with the interpretation of research results, and according to the judgement of the researchers, patients are classified as not eligible to participate in the study;
16. Other malignant tumors were diagnosed within 5 years before the first administration, excluding cured cutaneous basal cell carcinoma, cured squamous cell carcinoma and/or cured cancer in situ. If other malignant tumors or hepatocellular carcinomas are diagnosed more than five years before administration, pathological or cytological diagnosis should be taken from recurrent and metastasis sites;
17. Pregnancy and breastfeeding.

Primary outcomes:
measure: Progression-free survival
timeFrame: 6 months
Secondary outcomes:
measure: Overall survival
timeFrame: 12 months
measure: Objective response rate
timeFrame: 6 months
measure: Disease control rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
Study officials:
References: