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Trial Title:
Second-line Systemic Therapy Combined with SBRT for HCC with Oligoprogression After Standard First-line Systemic Treatment
NCT ID:
NCT06592612
Condition:
Hepatocellular Carcinoma
Oligoprogression
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Outcomes Assessor)
Intervention:
Intervention type:
Radiation
Intervention name:
SBRT and second-line systemic therapy
Description:
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.
Arm group label:
SBRT Arm
Intervention type:
Drug
Intervention name:
Second-line systemic therapy
Description:
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.
Arm group label:
Control Arm
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. 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. KPS (Karnofsky Performance Status) score ≥ 80;
2. Pathologically, or clinically diagnosed hepatocellular carcinoma (HCC) based on the
" Chinese Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma
(2024 Edition) ";
3. 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.
4. 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;
5. Child-Pugh score for liver function ≤ 7;
6. Estimated life expectancy greater than 3 months;
7. 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;
8. 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.
Exclusion Criteria:
1. Received first-line treatment other than bevacizumab combined with
atezolizumab/sintilimab or lenvatinib with or without PD-1 antibody;
2. Tumor progression within 3 months after first-line standard systemic therapy;
3. Experienced ≥ Grade 3 severe adverse reactions after first-line standard therapy;
4. Brain metastasis with hemorrhage at baseline or after first-line systemic therapy;
5. Previous radiotherapy to the site of the oligoprogressive lesion;
6. Active bleeding (e.g., hematemesis, hemoptysis) within 2 months before enrollment;
7. Received any other antitumor drug therapy or local treatment within 3 months before
enrollment;
8. 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;
9. 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;
10. Presence of autoimmune diseases or other conditions requiring long-term use of
steroids;
11. Known or suspected allergy to the study drugs or any drugs related to this trial;
12. History of organ transplantation;
13. Pregnant or breastfeeding women;
14. Other factors that may affect the patient's enrollment and assessment results;
15. Refusal to follow the follow-up requirements set by this study protocol or refusal
to sign the informed consent form.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
October 1, 2024
Completion date:
October 31, 2026
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06592612
