Hepatocellular CarcinomaPhase 2NCT06592612
Second-line Systemic Therapy Combined with SBRT for HCC with Oligoprogression After Standard First-line Systemic Treatment
A Phase 2 study testing SBRT and second-line systemic therapy and Second-line systemic therapy in people with Hepatocellular Carcinoma and Oligoprogression, run by Sun Yat-sen University.
Trial summary
Approximately 70% of hepatocellular carcinoma (HCC) patients are diagnosed at an advanced stage, with no opportunity for curative treatments. For these patients, systemic therapies are the main treatment modalities. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma, Oligoprogression
- What is being tested?
- SBRT and second-line systemic therapy and Second-line systemic therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2024to 31 Oct 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- KPS (Karnofsky Performance Status) score ≥ 80;
- Pathologically, or clinically diagnosed hepatocellular carcinoma (HCC) based on the \" Chinese Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2024 Edition) \";
- Patients with oligoprogression after first-line standard systemic therapy (bevacizumab combined with atezolizumab/sintilimab or lenvatinib with or without PD-1 antibody).
- Definition of oligoprogression: 1-5 progressive lesions involving 1-3 organs/systems, including: (1)The maximum diameter of a target lesion, as assessed by RECIST 1.1 criteria, increases by more than 20% compared to baseline, with an absolute increase of \>5 mm; (2) The maximum diameter of a target lesion increases by more than 20% compared to baseline on two consecutive evaluations (at least 2 months apart), regardless of whether the absolute increase is \>5 mm; (3) The appearance of a new intrahepatic lesion ≥1 cm with typical imaging characteristics of HCC; 4) The appearance of any new extrahepatic lesion or bone metastasis, regardless of size; 5) Any new FDG-avid lesion confirmed by PET/CT, or an increase in SUVmax of more than 30% with an absolute increase of \>0.8 SUV; 6) In the case of lymph node metastasis, each lymphatic drainage area is counted as one organ.
- All oligoprogressive lesions are deemed suitable for radiotherapy, with a maximum diameter of any single oligoprogressive lesion not exceeding 5 cm, and at least one measurable lesion (according to RECIST v1.1 criteria); bone metastases without soft tissue formation are eligible but considered non-measurable lesions; if bone metastases have soft tissue formation and meet measurable criteria, they are considered measurable lesions;
- Child-Pugh score for liver function ≤ 7;
Show all 9Show fewer
- Estimated life expectancy greater than 3 months;
- Function of essential organs meets the following criteria: white blood cells ≥ 3.0 × 10^9/L, neutrophils ≥ 1.5 × 10^9/L, platelets ≥ 50.0 × 10^9/L, hemoglobin ≥ 90 g/L; serum albumin ≥ 2.8 g/dL; total bilirubin ≤ 1.5 × ULN, ALT/AST/ALP ≤ 2.5 × ULN; serum creatinine ≤ 1.5 × ULN or creatinine clearance \> 60 mL/min; no severe organic disease;
- Participants must have the ability to understand and voluntarily sign a written informed consent form. Consent must be obtained before any specific study procedures begin, and the participant must agree to follow the medication and post-operative follow-up requirements outlined in the study design.
Who cannot join
- Received first-line treatment other than bevacizumab combined with atezolizumab/sintilimab or lenvatinib with or without PD-1 antibody;
- Tumor progression within 3 months after first-line standard systemic therapy;
- Experienced ≥ Grade 3 severe adverse reactions after first-line standard therapy;
- Brain metastasis with hemorrhage at baseline or after first-line systemic therapy;
- Previous radiotherapy to the site of the oligoprogressive lesion;
- Active bleeding (e.g., hematemesis, hemoptysis) within 2 months before enrollment;
Show all 15Show fewer
- Received any other antitumor drug therapy or local treatment within 3 months before enrollment;
- Severe impairment of the heart, lungs, kidneys, or other vital organs, active infections (other than viral hepatitis), or other severe comorbidities that make the patient unable to tolerate treatment;
- History of other malignancies, except for non-melanoma skin cancer, carcinoma in situ of the cervix, or early-stage prostate cancer that has been cured;
- Presence of autoimmune diseases or other conditions requiring long-term use of steroids;
- Known or suspected allergy to the study drugs or any drugs related to this trial;
- History of organ transplantation;
- Pregnant or breastfeeding women;
- Other factors that may affect the patient\'s enrollment and assessment results;
- Refusal to follow the follow-up requirements set by this study protocol or refusal to sign the informed consent form.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Second-line Systemic Therapy with or Without Stereotactic Body Radiotherapy (SBRT) for Oligoprogressive Hepatocellular Carcinoma After Standard First-line Systemic Treatment: a Prospective, Randomized, Phase II Study
Approximately 70% of hepatocellular carcinoma (HCC) patients are diagnosed at an advanced stage, with no opportunity for curative treatments. For these patients, systemic therapies are the main treatment modalities. However, the objective response rates of first-line systemic treatments are currently only 20-35%, and most patients inevitably develop drug resistance and disease progression during treatment, thus taking second-line therapies. Second-line treatment options include regorafenib, pembrolizumab, and others, but clinical studies have shown a median progression-free survival of only 2.6-3.1 months, indicating an urgent need to improve efficacy.
Stereotactic body radiotherapy (SBRT) has been widely used in recent years for curative treatment of early-stage liver cancer or as neoadjuvant and adjuvant therapy for patients with portal vein tumor thrombus. It is one of the important approaches in the multidisciplinary management of HCC. Researches have shown that SBRT has a synergistic effect with systemic drug therapy, potentially enhancing the efficacy of targeted and immunotherapies. Therefore, this study aims to conduct a prospective, randomized, controlled phase II clinical trial in patients with oligoprogressive HCC after standard first-line systemic treatment to evaluate whether adding SBRT to second-line systemic therapy can improve the efficacy of second-line treatment. The primary endpoint of the study is progression-free survival (PFS), while secondary endpoints include overall survival (OS), objective response rate (ORR), and treatment-related adverse events. We aim to comprehensively assess the effectiveness and safety of combining SBRT with second-line systemic therapy in treating oligoprogressive HCC patients.
- Conditions
- Hepatocellular Carcinoma, Oligoprogression
- Being tested
- SBRT and second-line systemic therapy, Second-line systemic therapy
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRT and second-line systemic therapyRadiation
Patients in the SBRT arm will receive second-line systemic therapy combined with SBRT. The choice and stipulations for second-line systemic therapy drugs are the same as those for the control arm.SBRT will be administered to all oligoprogressive lesions and must begin within 2 weeks after the start of second-line therapy. Systemic therapy will not be paused during SBRT. Patients who do not withdraw from the study will not receive crossover treatment; however, if a patient in the control group withdraws from the study due to tumor progression and is assessed as suitable for SBRT, salvage SBRT will be administered promptly.
Second-line systemic therapyDrug
Patients in the control arm will receive second-line systemic therapy. The following stipulations apply to the second-line treatment drugs: for patients who received bevacizumab combined with atezolizumab/sintilimab as the first-line treatment, lenvatinib or regorafenib will be used for second-line treatment; for patients who received lenvatinib with or without PD-1 antibody as the first-line treatment, regorafenib combined with another PD-1 antibody will be used for second-line treatment.
| Study group | Role | What they receive |
|---|---|---|
| Control Arm | Active comparator | Patients in the control arm will receive second-line systemic therapy until disease progression is confirmed by imaging or until they are unable to continue systemic therapy due to adverse events. The following stipulations apply to the second-line treatment drugs: for patients who received bevacizumab combined with atezolizumab/sintilimab as the first-line treatment, lenvatinib or regorafenib will be used for second-line treatment; for patients who received lenvatinib with or without PD-1 antibody as the first-line treatment, regorafenib combined with another PD-1 antibody will be used for second-line treatment. Receives: Drug: Second-line systemic therapy |
| SBRT Arm | Experimental | Patients in the SBRT arm will also receive second-line systemic therapy until disease progression is confirmed by imaging or until they are unable to continue systemic therapy due to adverse events. The choice and stipulations for second-line systemic therapy drugs are the same as those for the control arm. SBRT will be administered to all oligoprogressive lesions and must begin within 2 weeks after the start of second-line therapy. Systemic therapy will not be paused during SBRT. Patients who do not withdraw from the study will not receive crossover treatment; however, if a patient in the control group withdraws from the study due to tumor progression and is assessed as suitable for SBRT, salvage SBRT will be administered promptly. Receives: Radiation: SBRT and second-line systemic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival, PFS
PFS is defined as the time from treatment to the first confirmed disease progression based on imaging assessment according to the RECIST v1.1 criteria.
Measured: From date of treatment beginning until the date of follow-up completion, up to 2 year.
Secondary outcomes (3)
objective response rate，ORR
The ratio of patients achieving the best efficacy of the corresponding interventions, including complete response (CR) and partial response (PR), to all patients in the arm.
Measured: From date of treatment beginning until the date of follow-up completion, up to 2 year.
overall survival, OS
OS is defined as the time from treatment beginningto death from any cause
Measured: From date of treatment beginning until the date of follow-up completion, up to 2 year.
Incidence of adverse events (safety )
Treatment-related adverse events are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE 5.0)
Measured: From date of treatment beginning until the date of follow-up completion, up to 2 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start1 Oct 2024 (estimated)
- Primary completion31 Oct 2026 (estimated)
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chen Min-Shan, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06592612
- Sponsor's protocol ID
- B2024-428-01
- Status last verified
- Sep 2024
- First submitted
- 9 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Second-line Systemic Therapy with or Without Stereotactic Body Radiotherapy (SBRT) for Oligoprogressive Hepatocellular Carcinoma After Standard First-line Systemic Treatment: a Prospective, Randomized, Phase II Study
- ClinicalTrials.gov ID
- NCT06592612
- Acronym / sponsor ID
- B2024-428-01
- Conditions
- Hepatocellular Carcinoma, Oligoprogression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Oct 2024 (estimated)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approximately 70% of hepatocellular carcinoma (HCC) patients are diagnosed at an advanced stage, with no opportunity for curative treatments. For these patients, systemic therapies are the main treatment modalities. However, the objective response rates of first-line systemic treatments are currently only 20-35%, and most patients inevitably develop drug resistance and disease progression during treatment, thus taking second-line therapies. Second-line treatment options include regorafenib, pembrolizumab, and others, but clinical studies have shown a median progression-free survival of only 2.6-3.1 months, indicating an urgent need to improve efficacy.
Stereotactic body radiotherapy (SBRT) has been widely used in recent years for curative treatment of early-stage liver cancer or as neoadjuvant and adjuvant therapy for patients with portal vein tumor thrombus. It is one of the important approaches in the multidisciplinary management of HCC. Researches have shown that SBRT has a synergistic effect with systemic drug therapy, potentially enhancing the efficacy of targeted and immunotherapies. Therefore, this study aims to conduct a prospective, randomized, controlled phase II clinical trial in patients with oligoprogressive HCC after standard first-line systemic treatment to evaluate whether adding SBRT to second-line systemic therapy can improve the efficacy of second-line treatment. The primary endpoint of the study is progression-free survival (PFS), while secondary endpoints include overall survival (OS), objective response rate (ORR), and treatment-related adverse events. We aim to comprehensively assess the effectiveness and safety of combining SBRT with second-line systemic therapy in treating oligoprogressive HCC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Arm | Active comparator | Drug: Second-line systemic therapyPatients in the control arm will receive second-line systemic therapy until disease progression is confirmed by imaging or until they are unable to continue systemic therapy due to adverse events. The following stipulations apply to the second-line treatment drugs: for patients who received bevacizumab combined with atezolizumab/sintilimab as the first-line treatment, lenvatinib or regorafenib will be used for second-line treatment; for patients who received lenvatinib with or without PD-1 antibody as the first-line treatment, regorafenib combined with another PD-1 antibody will be used for second-line treatment. |
| SBRT Arm | Experimental | Radiation: SBRT and second-line systemic therapyPatients in the SBRT arm will also receive second-line systemic therapy until disease progression is confirmed by imaging or until they are unable to continue systemic therapy due to adverse events. The choice and stipulations for second-line systemic therapy drugs are the same as those for the control arm. SBRT will be administered to all oligoprogressive lesions and must begin within 2 weeks after the start of second-line therapy. Systemic therapy will not be paused during SBRT. Patients who do not withdraw from the study will not receive crossover treatment; however, if a patient in the control group withdraws from the study due to tumor progression and is assessed as suitable for SBRT, salvage SBRT will be administered promptly. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- KPS (Karnofsky Performance Status) score ≥ 80;
- Pathologically, or clinically diagnosed hepatocellular carcinoma (HCC) based on the \" Chinese Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2024 Edition) \";
- Patients with oligoprogression after first-line standard systemic therapy (bevacizumab combined with atezolizumab/sintilimab or lenvatinib with or without PD-1 antibody).
- Definition of oligoprogression: 1-5 progressive lesions involving 1-3 organs/systems, including: (1)The maximum diameter of a target lesion, as assessed by RECIST 1.1 criteria, increases by more than 20% compared to baseline, with an absolute increase of \>5 mm; (2) The maximum diameter of a target lesion increases by more than 20% compared to baseline on two consecutive evaluations (at least 2 months apart), regardless of whether the absolute increase is \>5 mm; (3) The appearance of a new intrahepatic lesion ≥1 cm with typical imaging characteristics of HCC; 4) The appearance of any new extrahepatic lesion or bone metastasis, regardless of size; 5) Any new FDG-avid lesion confirmed by PET/CT, or an increase in SUVmax of more than 30% with an absolute increase of \>0.8 SUV; 6) In the case of lymph node metastasis, each lymphatic drainage area is counted as one organ.
- All oligoprogressive lesions are deemed suitable for radiotherapy, with a maximum diameter of any single oligoprogressive lesion not exceeding 5 cm, and at least one measurable lesion (according to RECIST v1.1 criteria); bone metastases without soft tissue formation are eligible but considered non-measurable lesions; if bone metastases have soft tissue formation and meet measurable criteria, they are considered measurable lesions;
Key exclusion criteria (15 listed)
- Received first-line treatment other than bevacizumab combined with atezolizumab/sintilimab or lenvatinib with or without PD-1 antibody;
- Tumor progression within 3 months after first-line standard systemic therapy;
- Experienced ≥ Grade 3 severe adverse reactions after first-line standard therapy;
- Brain metastasis with hemorrhage at baseline or after first-line systemic therapy;
- Previous radiotherapy to the site of the oligoprogressive lesion;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SBRT and second-line systemic therapyPatients in the SBRT arm will receive second-line systemic therapy combined with SBRT. The choice and stipulations for second-line systemic therapy drugs are the same as those for the control arm.SBRT will be administered to all oligoprogressive lesions and must begin within 2 weeks after the start of second-line therapy. Systemic therapy will not be paused during SBRT. Patients who do not withdraw from the study will not receive crossover treatment; however, if a patient in the control group withdraws from the study due to tumor progression and is assessed as suitable for SBRT, salvage SBRT will be administered promptly. | Radiation | SBRT Arm |
| Second-line systemic therapyPatients in the control arm will receive second-line systemic therapy. The following stipulations apply to the second-line treatment drugs: for patients who received bevacizumab combined with atezolizumab/sintilimab as the first-line treatment, lenvatinib or regorafenib will be used for second-line treatment; for patients who received lenvatinib with or without PD-1 antibody as the first-line treatment, regorafenib combined with another PD-1 antibody will be used for second-line treatment. | Drug | Control Arm |
Primary outcome
progression-free survival, PFS
Time frame: From date of treatment beginning until the date of follow-up completion, up to 2 year.
PFS is defined as the time from treatment to the first confirmed disease progression based on imaging assessment according to the RECIST v1.1 criteria.
3 secondary outcomes
objective response rate，ORR
Time frame: From date of treatment beginning until the date of follow-up completion, up to 2 year.
overall survival, OS
Time frame: From date of treatment beginning until the date of follow-up completion, up to 2 year.
Incidence of adverse events (safety )
Time frame: From date of treatment beginning until the date of follow-up completion, up to 2 year.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: Yes
Related trials for Hepatocellular Carcinoma
Active, not recruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Active, not recruitingPhase 2
Combined Treatment of Durvalumab, Bevacizumab, Tremelimumab and Transarterial Chemoembolization (TACE) in Subjects With Hepatocellular Carcinoma or Biliary Tract Carcinoma
Hepatocellular Cancer, Hepatocellular Carcinoma
Active, not recruitingPhase 2
Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver
Metastatic Cholangiocarcinoma, Metastatic Hepatocellular Carcinoma
RecruitingPhase 2
Cabozantinib Combined With Ipilimumab/Nivolumab and TACE in Patients With Hepatocellular Carcinoma
Hepatocellular Carcinoma, HCC
RecruitingPhase 1
Neoadjuvant Hypofractionated Stereotactic Body Radiation Therapy Prior to Surgery for Hepatocellular Carcinoma: a Feasibility Study.
Hepatocellular Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SBRT and second-line systemic therapy and Second-line systemic therapy in people with Hepatocellular Carcinoma and Oligoprogression, run by Sun Yat-sen University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yaojun Zhang (+86 13719433968, zhangyuj@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression-free survival, PFS (time frame: From date of treatment beginning until the date of follow-up completion, up to 2 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024; AzTrials last refreshed its copy on 26 Oct 2026.