Malignant Ascites Clinical Trial
Official title:
A Phase Ia/Ib, Open-label, Single-arm, Dose-escalation and Expansion Study of Specific Dual-targeting VEGFR1 and PD-L1 CAR-T in Cancer Patients With Pleural or Peritoneal Metastases
Serosal cavity metastases of malignant tumor seriously affects the quality of life and survival time of patients with cancers in advanced stage. VEGFR1 is frequently expressed in breast cancer, ovarian cancer, lung cancer, gastric cancer and other malignant tumors and their metastases. The VEGFR1/PD-L1 dual-targeting CAR-T will be investigated in cancer patients with serosal cavity metastases.
Status | Recruiting |
Enrollment | 58 |
Est. completion date | December 31, 2024 |
Est. primary completion date | December 31, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: 1. Male or female, Age 18-65 years old; negative results of serum or urine pregnancy test within 48 hours before treatment are needed to provide for fertile women (or women who have undergone sterilization or at least 2 years after menopause can be regarded as infertile); 2. Patients diagnosed as ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, etc., accompanied by serous cavity metastasis, have received systemic standard treatment, and have clinical symptoms of serous cavity metastasis; 3. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-2; 4. Estimated life expectancy = 3 months (according to investigator's judgement); 5. Absolute neutrophil count = 1.5×10^9/L, platelet count = 90×10^9/L, absolute lymphocyte count =1×10^8/L, hemoglobin = 9.0 g/dL; 6. Creatinine clearance rate =60 mL/min, Serum ALT/AST=2.5 times of the normal level, and total bilirubin=1.5 times of the normal level; 7. Cardiac ejection fraction =50%, no pericardial effusion; 8. No other serious diseases (autoimmune diseases or any immune deficiency disease or other disease in need of immunosuppressive therapy); 9. Patients must stop chemotherapy and targeted therapy for at least 3 weeks before starting treatment; 10. Patients must take reliable contraceptive measures before entering the trial, during the research process until 1 year after CAR-T infusion; reliable contraceptive measures will be determined by the main investigator or designated personnel; 11. Voluntarily participate in the research, understand and sign the informed consent; 12. The side effect of the last anti-tumor treatment was reduced to =1 grade, except for hair loss. Exclusion Criteria: 1. Had accepted any treatment of CAR-T therapy; 2. Allergic to cytokines; uncontrolled activity infection; 3. Acute or chronic (graft-versus-host disease) GVHD; 4. Accompanied by other uncontrolled malignant tumors; 5. Patient with hepatitis B or C active period, HIV infection = the upper limit of the normal level; 6. Other uncontrolled diseases in active period that hinder participation in the trial; 7. Suffer from serious diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, etc.; 8. Patients with grade 2-3 hypertension or poorly controlled; 9. History of mental illness that is difficult to control; 10. Patients have used immunosuppressive agents for a long time after organ transplantation, except for recent or current inhaled corticosteroid therapy; 11. The existing medical history or mental state history or laboratory abnormalities may increase the risk associated with participating in the study or the administration of the study drug from the point view of PI; 12. Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment. If receiving anticoagulant therapy; 13. Pregnant or nursing women, or plan to become pregnant during the treatment period or within 1 year after the treatment ends; 14. Female subjects of childbearing age were reluctant to accept high-efficiency contraceptive measures during the treatment period or within 1 year after the treatment ends; 15. Patient suffering from diseases that have signed written informed consent or comply with research procedures; or are unwilling or unable to comply with research requirements; 16. Patients who are inappropriate to participate in this experiment as considered by PI. |
Country | Name | City | State |
---|---|---|---|
China | West China Hospital, Sichuan University | Chengdu | Sichuan |
Lead Sponsor | Collaborator |
---|---|
Sichuan University |
China,
Cheema PK, Burkes RL. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer. Curr Oncol. 2013 Apr;20(2):e150-60. doi: 10.3747/co.20.1226. — View Citation
Wagner DL, Fritsche E, Pulsipher MA, Ahmed N, Hamieh M, Hegde M, Ruella M, Savoldo B, Shah NN, Turtle CJ, Wayne AS, Abou-El-Enein M. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021 Jun;18(6):379-393. doi: 10.1038/s41571-021-00476-2. Epub 2021 Feb 25. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | AEs will be recorded and evaluated by CTCAT 5.0. | Safety | 28 days | |
Primary | Recommended phase II dose (RP2D). | Efficacy dose | Approximately 18 months. | |
Primary | Therapeutic efficacy will be evaluated according to RECIST1.1. | Ant-tumor effects | Approximately 18 months. | |
Primary | Dose-limiting toxicity (DLT) will be assessed by CTCAE 5.0. | Tolerability evaluation | 28 days | |
Secondary | Objective Remission Rate (ORR). | Include CR (complete response) and PR (partial response). | 3 months | |
Secondary | Progression-Free Survival (PFS ). | The time from CAR-T administration to disease progression or death. | Approximately 18 months. | |
Secondary | Duration Of Control Rate (DCR). | The number of cases in which response (PR + CR) and stable disease (SD) are achieved from the start of cell infusion/the total number of evaluable cases (%). | 3 months | |
Secondary | Duration Of Response (DOR). | It refers to the time from the first evaluation of CR or PR to the first evaluation of PD(Progressive Disease) or death from any reason. | Approximately 18 months. | |
Secondary | Overall-Survival (OS). | It defined as the time from randomization to death from any cause, is a direct measure of clinical benefit to a patient. Patients alive or lost to follow-up are censored. | Approximately 18 months. | |
Secondary | Anti-CAR antibody production | Immunogenicity | 12 months. | |
Secondary | CAR-T cell numbers. | PK/PD | 12 months. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06200376 -
A Clinical Study of Intraperitoneal T3011 Given as a Single Agent in Patients With Malignant Ascites Induced by Advanced Colorectal Cancer
|
Phase 1 | |
Completed |
NCT04051112 -
Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Malignant Ascites
|
Phase 1 | |
Completed |
NCT00836654 -
Study in EpCAM Positive Patients With Symptomatic Malignant Ascites Using Removab Versus an Untreated Control Group
|
Phase 2/Phase 3 | |
Not yet recruiting |
NCT05501340 -
PD-1 Inhibitor Intraperitoneal Perfusion Combined With PRaG Therapy for Malignant Ascites
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT03550560 -
EUS-Guided Drainage of Refractory Malignant Ascites
|
||
Recruiting |
NCT04501744 -
A Study of M701 (EpCAM and CD3) in Malignant Ascites
|
Phase 1 | |
Terminated |
NCT00028782 -
EF5 in Detecting Oxygen Level and Blood Vessels in Tumor Cells of Patients Undergoing Photodynamic Therapy for Intraperitoneal or Pleural Cancer
|
N/A | |
Active, not recruiting |
NCT06266091 -
Treat Malignant Ascites Caused by Gastrointestinal or Ovarian Cancer With M701 Bispecific Antibody
|
Phase 2 | |
Withdrawn |
NCT04076566 -
Malignant Ascites Alfapump® Study
|
||
Enrolling by invitation |
NCT01854866 -
Safety and Effectiveness Study of Tumor Cell-derived Microparticles to Treat Malignant Ascites and Pleural Effusion
|
Phase 2 | |
Recruiting |
NCT03230708 -
Clinical Study of Autologous Erythrocytes Derived MPs Packaging MTX Peritoneal Perfusion to Treat Malignant Ascites
|
Phase 1/Phase 2 | |
Completed |
NCT01327235 -
Endostar and/or Cisplatin for Treatment of Malignant Pleural Effusion or Ascites
|
Phase 2 | |
Recruiting |
NCT06432296 -
Treatment of Malignant Ascites Caused by Advanced Epithelial Solid Tumors With M701 Bispecific Antibody
|
Phase 3 | |
Not yet recruiting |
NCT04985357 -
Defining the Clinical Potential of Mass Response as a Biomarker for Patient Tumor Sensitivity to Drugs
|
||
Terminated |
NCT02496286 -
Feasibility Study of Intraperitoneal Bevacizumab for Palliation of Intractable Malignant Ascites
|
Phase 1 | |
Completed |
NCT01532427 -
ALFApump System Post Marketing Surveillance Registry
|
||
Completed |
NCT00326885 -
Study of the Trifunctional Antibody Catumaxomab to Treat Recurrent Symptomatic Malignant Ascites
|
Phase 2 | |
Recruiting |
NCT02530398 -
A Tolerance Trial of Cinobufacini Injection Intraperitoneal Perfusion on Digestive System Cancer With Ascites
|
Phase 1 | |
Withdrawn |
NCT00908219 -
A Study of Bevacizumab to Prevent Malignant Ascites
|
Phase 2 | |
Recruiting |
NCT06016179 -
Tocilizumab Delivered Via Pleural and Peritoneal Catheters in Patients With Advanced Metastatic Cancer
|
Phase 1 |