Triple Therapy Sequential Radiotherapy in Unresectable HCC (TALENP003)

August 18, 2024 updated by: Shao-Ming Wei, Fujian Provincial Hospital

A Single-arm, Phase II, Prospective Study of Transcatheter Arterial Chemoembolization, Lenvatinib Combination With Sintilimab Sequential Radiotherapy in Patients With Initial Unresectable Hepatocellular Carcinoma

This is an Open-label, Multicenter, Phase II clinical trial to evaluate the efficacy and safety of Transcatheter arterial chemoembolization (TACE), Lenvatinib combination with Sintilimab (Triple Therapy) sequential radiotherapy in patients with Unresectable Hepatocellular Carcinoma (uHCC).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

For Unresectable Hepatocellular Carcinoma (uHCC) patients, Transcatheter arterial chemoembolization (TACE), Lenvatinib combined with PD-1 inhibitors treatment is an important choice, which can achieve deeper tumor remission. However, there are still some patients whose lesions have not reached complete response after treatment. According to research, patients with complete response of lesions after conversion therapy have a more ideal long-term survival rate. For populations that have not yet achieved complete response, sequential radiotherapy will achieve deeper tumor remission, delay recurrence, and achieve better oncological outcomes. This study is a single arm, multicenter, prospective clinical trial designed to evaluate the efficacy and safety of TACE, Lenvatinib combination with Sintilimab (Triple Therapy) sequential radiotherapy in the treatment of uHCC patients.

Study Type

Observational

Enrollment (Estimated)

28

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Shao-Ming Wei
  • Phone Number: (+86)13599037493
  • Email: 67468424@qq.com

Study Locations

  • China
    • Fujian
      • Fuzhou, Fujian, China
        • Not yet recruiting
        • Fujian Provincial Hospital
        • Contact:
      • Fuzhou, Fujian, China
        • Recruiting
        • Fujian Provincial Hospital
        • Contact:
      • Fuzhou, Fujian, China
        • Not yet recruiting
        • Mengchao Hepatobiliary Hospital of Fujian Medical University
        • Contact:
      • Fuzhou, Fujian, China
        • Not yet recruiting
        • First Affiliated Hospital of Fujian Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Unresectable Hepatocellular Carcinoma

Description

Inclusion Criteria:

  1. Be willing and able to enrollment in this study, signing the informed consent form;
  2. Age between 18 and 75 years old, male or female patients;
  3. Child-Pugh class A;
  4. Indocyanine green 15 min retention rate (ICGR-15) <15%;
  5. ECOG score 0-1;
  6. Diagnosis of hepatocellular carcinoma according to the Chinese HCC Diagnosis and Treatment Guidelines 2022 Edition and expected survival time greater than 4 months.
  7. Patients with a diagnosis of initial unresectable HCC (BCLC stage B or C), evaluated as partial response (PR) or stable disease (SD) by RECIST 1.1 after 2 months of treatment with TACE, Lenvatinib combination with Sintilimab. The number of residual active lesions in the liver was 1 to 3 and suitable for radiation therapy. Fusion lesions in the liver were considered as 1 lesion, and portal vein cancer thrombus was considered as 1 lesion for treatment.
  8. Normal tissue limits were performed according to the UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy.
  9. Patients who have not received any tumor-related targeted, immunotherapy, radiotherapy and chemotherapy before enrollment;
  10. Patients with at least one measurable lesion according to RECIST 1.1 criteria (measurable lesion CT/MRI scan length diameter ≥10mm, and measurable lesion has not received localized treatments such as radiotherapy, cryotherapy, etc.);
  11. Blood routine: absolute neutrophil count ≥1.5×10^9/L, Hb ≥8.5g/L, PLT ≥75×10^9/L;
  12. No history of severe cardiac arrhythmia or heart failure; no history of severe ventilatory dysfunction or severe pulmonary infection; no acute or chronic renal failure with creatinine clearance >40 mL/min;
  13. Women of childbearing age should agree that they must use contraception during and for 6 months after the end of the dosing period; patients who have had a negative serum or urine pregnancy test within 7 days prior to study enrollment and must be non-lactating, and men should agree that they must use contraception during and for 6 months after the end of the study period.

Exclusion Criteria:

  1. Patients with a diagnosis of initial unresectable HCC, assessed as complete response (CR) or Progressive disease (PD) by RECIST 1.1 after 2 months of treatment with TACE, Lenvatinib combined with Sintilimab;
  2. Tumor combined with cancerous thrombus in the inferior vena cava and the tumor has developed extrahepatic metastasis;
  3. Treatment with other antitumor therapy such as targeted drugs, PD-1/PD-L1 inhibitors, surgery, TACE, radiotherapy, FOLFOX systemic chemotherapy, and locus coeruleus granule drugs prior to study entry;
  4. History of allergy to Lenvatinib, Sintilimab and their components;
  5. Tumor volume accounting for two-thirds or more of the liver volume or diffuse distribution of intrahepatic lesions;
  6. Presence of any active autoimmune disease or patients with autoimmune disease with expected relapse (e.g., interstitial pneumonitis, colitis, hepatitis, pituitary gland inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including, but not limited to, these disorders and syndromes); hypothyroidism treated with stabilized doses of thyroid-replacing hormone; 1-year old diabetes mellitus using stabilized doses of insulin; or Type 1 diabetes mellitus; but not vitiligo or resolved childhood asthma/allergies that do not require any intervention in adulthood;
  7. Patients have history of immunodeficiency; patients who are on immunosuppressive or systemic hormone therapy for immunosuppression and have continued to do so within 2 weeks prior to signing the informed consent form
  8. Have known hereditary or acquired bleeding (e.g., coagulation disorders) or thrombotic tendencies, such as in patients with hemophilia; current or recent (within 10 days prior to initiation of study treatment) use of full-dose oral or injectable anticoagulant or thrombolytic medications for therapeutic purposes (prophylactic use of low-dose aspirin, low-molecular heparin is permitted)
  9. Severe infections (CTCAE > Grade 2) such as severe pneumonia requiring hospitalization, bacteremia, or infectious co-morbidities within 4 weeks prior to the first dose of study drug; baseline chest imaging suggestive of active lung inflammation, signs and symptoms of infection within 2 weeks prior to the first dose of study drug, or requiring treatment with oral or intravenous antibiotics (excluding prophylactic antibiotics). (excluding prophylactic use of antibiotics);
  10. Patients with proteinuria with routine urinalysis suggestive of ≥ 1 + will undergo a 24-hour urine protein test for 24-hour urine protein ≥ 1g;
  11. Have history of other malignant tumors within the previous 5 years or concurrently, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix and papillary thyroid carcinoma;
  12. Patients with co-morbid mental diseases; history of psychotropic substance abuse, alcoholism and drug addiction;
  13. Women who are pregnant or breastfeeding
  14. Patients with obvious contraindications to surgery, such as renal and cardiopulmonary insufficiency, as judged by the investigator, and those who, in the opinion of the investigator, should not participate in this trial for other reasons.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Triple Therapy sequential Radiotherapy
Combination product: TACE, Lenvatinib combination with Sintilimab sequential radiotherapy
TACE, Lenvatinib [8mg(<60kg)/12mg(>60kg) orally daily] combination with Sintilimab (200mg administered intravenous injection on Day 1 of each 21-day cycle) for 2 months. Sequential radiotherapy method and dosage are comprehensively evaluated by radiologists, hepatobiliary surgeons, and oncologists, and discussed by a multidisciplinary team

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate, ORR
Time Frame: 4 weeks after the initiation of medication until the day before surgery
The objective response rate (ORR) was defined as the complete response (CR) rate + the partial response (PR) rate according to RECIST 1.1.
4 weeks after the initiation of medication until the day before surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival, PFS
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
The Progression free survival (PFS) was defined as the time between the start of treatment and the progression of intrahepatic and/or extrahepatic tumors, or the occurrence of death or loss of follow-up for any reason.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Overall survival, OS
Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months
The Overall survival (OS) was defined as the time between receiving treatment and observing death or loss of follow-up for any reason.
From date of randomization until the date of death from any cause, whichever came first, assessed up to 60 months
Objective response rate, ORR
Time Frame: 4 weeks after the initiation of medication until the day before surgery
The objective response rate (ORR) was defined as the complete response (CR) rate + the partial response (PR) rate according to mRECIST.
4 weeks after the initiation of medication until the day before surgery
Conversion resection rate, CRR
Time Frame: 3 months
The Conversion resection rate (CRR) was defined as the patient who reach the resectable criterion after treatment and accepted operation.
3 months
Major pathological response rate, MPR rate
Time Frame: Immediately after surgery
The major pathological response (MPR) rate was defined as less than 10% active tumor cells in the excised tissue sample in patients accept operation.
Immediately after surgery
Toxicity Adverse events
Time Frame: through study completion, assessed up to 60 months
Grade 1-5 AEs according to NCI-CTCAE V5.0.
through study completion, assessed up to 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fujian Provincial Hospital

Investigators

  • Principal Investigator: Shao-Ming Wei, Fujian Provincial Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 15, 2024

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2028

Study Registration Dates

First Submitted

July 13, 2024

First Submitted That Met QC Criteria

August 18, 2024

First Posted (Actual)

August 20, 2024

Study Record Updates

Last Update Posted (Actual)

August 20, 2024

Last Update Submitted That Met QC Criteria

August 18, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TALENP003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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