Radiotherapy for patients with oligoprogressive liver cancer after PD-1 therapy

Efficacy and Safety of Radiotherapy in Oligoprogressive HCC Following First-line PD-1 Therapy: A Phase II Clinical Study

This study is testing if adding radiation therapy can help people with liver cancer who have had some success with PD-1 therapy but are starting to see their cancer progress.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (other)
• Drugs / interventions: prednisone
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06870942 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of radiotherapy in patients with oligoprogressive hepatocellular carcinoma (HCC) who have previously undergone first-line PD-1 therapy. It focuses on patients who have stable disease for at least three months and presents with five or fewer lesions across three or fewer organs. The goal is to determine if local radiotherapy can help overcome resistance to immune checkpoint inhibitors and delay the need for changes in systemic therapy. Participants will receive maintenance treatment alongside radiation therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with oligoprogressive HCC after first-line PD-1 therapy and stable disease for at least three months.

Not a fit: Patients with extensive disease progression beyond oligoprogression or those with a history of irradiation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with oligoprogressive HCC, potentially improving their outcomes and delaying disease progression.

How similar studies have performed: While the use of radiotherapy in this context is gaining interest, the specific approach of combining it with PD-1 therapy in oligoprogressive HCC is relatively novel and has not been extensively tested in prior studies.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Shu-jung Hsu

Conditions: HCC - Hepatocellular Carcinoma, Radiotherapy