Muscle-invasive urothelial carcinoma (MIUC)
Conditions
Interventions
Group 1 :Anlotinib plus cisplatin and gemcitabine (CG)
Group 2:Anlotinib + penpulimab
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age 18-75 years old; 2. Histological diagnosis of muscle-invasive urothelial carcinoma (bladder, urethra, ureter or renal pelvis tumor) is suitable and planned for radical resection (according to local guidelines); 3. CT (or MRI) + PET/CT (RECISTv1.1, within 4 weeks) of clinical stage T1-T4N1-3M0, T3-4N0M0; 4. There are archived formalin-fixed paraffin-embedded (FFPE) tumor specimens (preferred block) or at least 10 unstained tissue sections and relevant pathology reports for evaluating tumor PD-L1 expression; if there are no sections, Biopsy tissue is strongly recommended; 5. At least one measurable lesion according to RECIST 1.1; 6. Eastern Cooperative Oncology Group (ECOG) score status 0-1; 7. Complete hematology and end-organ function tests within 7 days before enrollment: (1) Hemoglobin >= 9.0 g/d; (2) Absolute neutrophil count (ANC) >= 1.5 x 10^9/L; (3) Platelet count >= 80 x 10^9/L; (4) Serum bilirubin = 60 ml/min; (7) Partial thrombin time/prothrombin time (PTT/PT) = 50%; 8. Women of childbearing age who have a negative serum pregnancy test (subjects with reproductive potential) within 7 days before treatment must agree to use high-efficiency methods of contraception before, during, and within 6 months after the last dose of study treatment; Negative serum or urine pregnancy test within 7 days before study enrollment, and must be a non-lactating subject; 9. Volunteer to participate in this study and sign the informed consent; 10. Good compliance; 11. In addition to the above inclusion criteria: (1) Cohort 1-anlotinib + gemcitabine/cisplatin: 1) Hearing impairment <= level 1; 2) Peripheral neuropathy <= Grade 1; (2) Cohort 2-anlotinib + pembrolizumab: patients with positive PD-L1 expression in tissue detection.
Exclusion criteria
Exclusion criteria: 1. With metastatic disease (M1); 2. Previously received systemic chemotherapy, anti-angiogenic targeted small molecule therapy or radiotherapy for urothelial carcinoma; 3. Previously received programmed death-1/programmed death ligand-1 (PD-1/PD-L1), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or any other targeted T cells Drug therapy for co-stimulatory or immune checkpoint pathways; 4. The patient is using immunosuppressants, except for the following: (1) Intranasal, inhaled, topical steroids, or topical steroid injections (eg, intra-articular injections); (2) Physiological dose = grade 2); however, hair loss or other grades below 2 that do not constitute a safety risk according to the investigator's judgment are acceptable; 7. The patient has any active autoimmune disease, which may worsen when receiving immune stimulants; 8. There are multiple factors that affect the absorption of oral drugs (such as inability to swallow, post-gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.); 9. Imaging studies show that the tumor invades large blood vessels or the investigator judges that the tumor is very likely to invade important blood vessels during the follow-up study and cause fatal massive hemorrhage; 10. Hemoptysis occurred within 1 month before the first administration, the maximum daily hemoptysis volume >= 2.5 mL or clinically significant bleeding symptoms or clear bleeding tendency; 11. Arterial/venous thrombosis within 6 months before enrollment; 12. Uncontrolled hypertension, defined as systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg, which cannot be well controlled by antihypertensive drug therapy; 13. Major cardiovascular disease, New York Heart Association (NYHA) grade 2 or above, myocardial infarction, clinically significant arrhythmia or severe/unstable angina within 3 months before enrollment; 14. There is evidence of serious uncontrolled concomitant diseases that may affect the compliance with the protocol or the interpretation of the study results, including uncontrolled diabetes, history of related lung diseases (eg, immune pneumonia, pulmonary fibrosis), inability to controlled major epileptic disorders, or superior vena cava syndrome; 15. The history of attenuated live vaccine vaccination within 28 days before the first study medication or the expected attenuated live vaccine vaccination during the study period; 16. Known human immunodeficiency virus (HIV) infection or known history of acquired immunodeficiency syndrome; 17. Active hepatitis, including hepatitis B (such as HBsAg reaction), hepatitis C (such as detection of HCV RNA) or co-infection of hepatitis B and C; 18. Severe infection within 4 weeks before the first administration, including but not limited to bacteremia and severe pneumonia requiring hospitalization; 19. Received major surgical treatment within 4 weeks before enrollment or expected to undergo major surgery during the study except for diagnosis; 20. Previously or planning to receive organ transplantation, including
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pathological Complete Response Rate (pCR);Disease-Free Survival (DFS);Overall Survival (OS);Safety; | — |
Countries
China
Contacts
Public ContactYe Dingwei
Fudan University Shanghai Cancer Center
Outcome results
None listed