Maintaining First-Line Therapy Plus Radiation Therapy May Prolong Progression-Free Survival and Delay Second-Line Therapy for Oligoprogressive Hepatocellular Carcinoma.
Boyu Leng, Haohua Wang, Yunfan Ge...
https://pubmed.ncbi.nlm.nih.gov/39824367Actively Recruiting
Phase 3
Age: 18Years - 75Years
All Genders
ID06841172
Continuation of First-line Therapy With Radiotherapy for Oligoprogression Versus Early Switch to Second-line Therapy in Oligoprogressive Hepatocellular Carcinoma (CROSS): a Multi-center, Randomized, Controlled, Open-label, Phase III Trial
Led by Shandong Cancer Hospital and Institute · Updated on 2025-08-01
132
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This research aims to evaluate treatment options for patients with oligoprogressive hepatocellular carcinoma (HCC) who are receiving first-line systemic therapy. HCC is often diagnosed late due to its aggressive nature and lack of early symptoms, limiting curative options. The study compares whether adding radiotherapy to treat limited progressing lesions while continuing first-line therapy can extend progression-free survival compared to switching early to second-line systemic therapy. This is a multicenter, randomized, controlled, open-label Phase III trial. Participants will be assigned to one of two groups: one group will continue their current first-line systemic therapy, which may include combinations like atezolizumab plus bevacizumab or monotherapies such as lenvatinib or sorafenib, combined with radiotherapy targeting the progressing lesions. Radiotherapy will use techniques such as 3D-CRT, IMRT, or IGRT with a biologically effective dose of at least 60 Gy, adjusted by tumor location and size. The other group will switch early to second-line systemic therapy, individualized by a multidisciplinary team based on prior treatment and patient condition. During the study, participants will have regular assessments including imaging to confirm progression, tumor and blood sample collection for biomarker analysis, and monitoring for adverse events. The primary outcome is progression-free survival measured over two years, with secondary outcomes including overall survival, response rates, and safety over up to five years. Follow-up includes evaluation of circulating tumor DNA and optional biopsies to explore molecular changes. Participants are expected to comply with treatment and follow-up visits throughout the study duration.
CONDITIONS
Brief Title
Continuation of First-line Therapy With Radiotherapy Versus Early Switch to Second-line Therapy in Oligoprogressive HCC
Who Can Participate
Age: 18Years - 75Years
All Genders
Eligibility Criteria
You may qualify if you...
- Histological or cytological confirmation of primary hepatocellular carcinoma or diagnosis based on national clinical guidelines.
- BCLC stage C at the start of first-line systemic treatment.
- Confirmed oligoprogression during first-line systemic therapy with 1-5 progressing lesions in no more than 1-3 organs.
- Current first-line systemic therapy must have controlled disease for at least 3 months before oligoprogression.
- Oligoprogressive lesions must be eligible for radiotherapy and include at least one measurable lesion per RECIST v1.1.
- Liver function assessed as Child-Pugh score 7 points or less.
- ECOG Performance Status score of 0 or 1.
- Ability to understand and voluntarily sign informed consent and comply with study procedures.
- Male or female patients aged between 18 and 75 years.
- Availability of tumor and blood samples for biomarker assessment.
You will not qualify if you...
- Patients who received first-line systemic therapy as adjuvant treatment after curative surgery for HCC.
- Tumor progression within 3 months after starting first-line systemic therapy.
- Combined hepatocellular-cholangiocarcinoma diagnosis.
- History of grade 3 or higher serious adverse events caused by first-line systemic therapy.
- Presence of brain, peritoneal, or omental metastases with bleeding after first-line systemic therapy.
- Prior radiation therapy to the site of oligoprogressive lesions.
- Active untreated hepatitis B infection with high viral DNA levels.
- Oligoprogressive lesions not suitable for radiotherapy.
- Alpha-fetoprotein levels above 10,000 ng/mL at oligoprogression.
- Diagnosis of other malignancies within 3 years before enrollment, except certain skin cancers.
- Participation in other interventional clinical trials or investigational treatments within 4 weeks before enrollment.
- Autoimmune diseases or conditions requiring long-term steroid use.
- Severe impairment of major organs or active infections other than viral hepatitis.
- Known allergy to study drugs or related medications.
- History of organ transplantation.
- Pregnant or breastfeeding women.
- Any other factor that may affect patient enrollment or study evaluation as judged by the investigator.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Until disease progression or discontinuation
Participants receive either continued first-line systemic therapy combined with radiotherapy targeting oligoprogressive lesions, or an early transition to second-line systemic therapy. Radiotherapy is administered to oligoprogressive lesions with a biologically effective dose (BED) ≥60 Gy. Systemic therapy includes various approved drug regimens based on prior treatments and physician discretion.
Visits scheduled according to treatment protocols and monitoring requirements
Follow-up
Duration - Up to 5 years
Participants are monitored for progression-free survival, overall survival, adverse events, and treatment response for up to 5 years after treatment initiation.
Regular follow-up visits as per study schedule
Trial Site Locations
Total: 1 location
1
Jinan, Shandong 0531
Jinan, Shandong, China
Actively Recruiting
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Research Team
J
Jinbo Yue, Doctor
J
Jinbo Yue, Doctor
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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Published Research Related To This Trial
Efficacy of stereotactic ablative radiotherapy in patients with oligometastatic hepatocellular carcinoma: A phase II study.
Seo Hee Choi, Byung Min Lee, Jina Kim...
https://pubmed.ncbi.nlm.nih.gov/38467379Systematic review of the efficacy of stereotactic ablative radiotherapy for oligoprogressive disease in metastatic cancer.
Emma Doyle, Angus J Killean, Stephen Harrow...
https://pubmed.ncbi.nlm.nih.gov/38648995Stereotactic ablative radiotherapy for oligoprogressive solid tumours: A systematic review and meta-analysis.
Vivian S Tan, Jerusha Padayachee, George B Rodrigues...
https://pubmed.ncbi.nlm.nih.gov/39197501Sequencing of systemic therapy in unresectable hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis of randomized clinical trials.
Qi Wang, Jianan Yu, Xuedong Sun...
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Josep M Llovet, Florian Castet, Mathias Heikenwalder...
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Daniela F Quail, Johanna A Joyce
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