Lenalidomide to Reverse Drug Resistance After First-line Treatment of Advanced HCC

• Status: Not yet recruiting
• Trial end date: 2025-10-05
• Target enrollment: 0
• Participant gender: All

Summary

The ORR of the lenvatinib combination (lenvatinib combined with PD-1 inhibitor) was largely similar to that of the "A+T" combination (bevacizumab and atelelizumab). The disease control rate (DCR) for the combination of lenvatinib was 88%, demonstrating the efficacy of lenvatinib in combination with immunotherapy. However, progression to second-line therapy after first-line treatment for advanced HCC still faces many challenges.

In our clinical practice and review of the literature, we focused on lenalidomide showing some efficacy in second-line treatment of advanced HCC. Lenalidomide is a new generation derivative of thalidomide, which has dual anti-angiogenic and immunomodulatory anti-tumor effects. Lenalidomide may have the potential to reverse drug resistance and increase the efficacy of synergistic immune-targeted therapy. Based on the preliminary data of its effectiveness in the second-line treatment of advanced HCC alone or in combination with TKI, we propose to conduct a prospective, exploratory, single-arm, open, multicenter phase II clinical study of advanced HCC PD-1 inhibitor in combination with lenvatinib after progression of first-line treatment, to initially evaluate the efficacy and safety of this regimen.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shenyang Tenth People's Hospital
• Collaborator: Beijing Tsinghua Changgeng Hospital
• Treatments: Lenalidomide

Criteria

Inclusion Criteria:

1. Willing and able to sign a written informed consent;

2. Age ≥ 18 and ≤ 75 years old on the day of signing the informed consent form;

3. Locally advanced hepatocellular carcinoma, clinical diagnosis of hepatocellular carcinoma by histology/cytology, imaging (enhanced MRI or enhanced CT or PET-CT);

4. Advanced metastatic and/or unresectable HCC progresses after combination therapy with lenvatinib combined with PD-1 inhibitors (must be domestically approved for use in liver cancer);

5. Eastern Cooperative Oncology Group (ECOG) physical status score is 0 or 1;

6. Liver function in line with Child-Pugh A grade (score 5-6 points);

7. Hepatitis B surface antigen detection is required before enrollment. For patients who are confirmed to have hepatitis B, antiviral drugs should be started 1 week before treatment;

8. During the study screening period, patients must be tested for hepatitis C virus (HCV) RNA status. This study allowed for the study of patients with untreated chronic HCV infection. In addition, patients who have been cured of hepatitis C can be included in this study, but the hepatitis C treatment should be completed for more than 4 weeks at the time of enrollment;

9. The main organ functions are basically normal and meet the following requirements:

Bone marrow: absolute neutrophil count ≥1.5×109/L, platelet ≥50×109/L, hemoglobin ≥90g/L.

Liver: total bilirubin ≤ 2 times the upper limit of normal (ULN), aspartate aminotransferase and alanine aminotransferase ≤ 5 × ULN, albumin ≥ 29 g/L.

Kidney: serum creatinine ≤1.5×ULN, or creatinine clearance ≥50mL/min. Coagulation function: international normalized ratio (INR) ≤ 2, and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN.

10. The expected survival time is more than 3 months;

11. Patients with other malignant tumors have lived disease-free for more than 2 years after initial treatment (such as non-melanoma skin cancer or cervical cancer in situ);

12. Women of childbearing age must agree to use effective contraception for at least 4 weeks before enrollment in the study, during the study and within 4 weeks after the withdrawal of the study drug. Women of childbearing potential require a serum pregnancy test within 72 hours of starting treatment. Male subjects must also use effective contraception during treatment and within 4 weeks of drug withdrawal. The spouse of the subject also needs to do a good job of contraception during the subject's participation in the study;

13. Did not participate in other clinical trials within 4 weeks before screening; those who failed to screen in other trials but met the requirements of this trial can be enrolled.

Exclusion Criteria:

1. Hypersensitivity to iridamine drugs;

2. Fibrolamellar or sarcomatoid HCC;

3. Mixed HCC-ICC;

4. Currently participating in and receiving other experimental treatments, or participating in a study of immune checkpoint inhibitors and receiving study treatment;

5. Previous solid organ transplantation, diagnosed as immunodeficiency, or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first trial treatment;

6. Esophageal or gastric variceal bleeding within 3 months before enrollment;

7. Hepatic encephalopathy in the past 6 months, or obvious ascites at the time of enrollment;

8. Have a known history of active tuberculosis;

9. Hypersensitivity to PD-1 inhibitors;

10. The subject has other known aggressive malignant tumors at the same time (except for those who have no evidence of tumor recurrence after treatment and the duration is more than 2 years). Exceptions include: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, low-risk prostate cancer, or cervical cancer in situ;

11. Patients with previous active autoimmune diseases requiring systemic treatment;

12. History or any evidence of known active non-infectious pneumonia;

13. Active infection requires systemic treatment;

14. People with known mental illness or substance abuse disorder;

15. Pregnant or lactating women;

16. Known human immunodeficiency virus (HIV) medical history (HIV 1/2 antibody);

17. Have been vaccinated with live vaccines within 30 days before starting the study treatment;

18. Those who suffer from high blood pressure and cannot be well controlled by antihypertensive drug treatment (systolic blood pressure>140mmHg, diastolic blood pressure>100mmHg); suffer from myocardial ischemia or myocardial infarction above CTCAE grade II, poorly controlled arrhythmia, And/or New York Heart Association (NYHA) class III~IV cardiac insufficiency;

19. Other conditions that the investigator believes prevent patients from participating in this trial.