Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05979740
Other study ID # LY2023-002-A
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date August 1, 2023
Est. completion date February 13, 2024

Study information

Verified date August 2023
Source RenJi Hospital
Contact Haige Chen
Phone 02168383575
Email kirbyhaige@aliyun.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a prospective, open, single-center clinical study of RC48 combined with PD-1 and radiotherapy as bladder-preserving therapy in patients with muscular invasive bladder uroepithelial carcinoma with high HER-2 expression (IHC 2+ or 3+). The study was conducted in accordance with the Good Practice for Clinical Trials of Pharmaceutical Products (GCP). Six patients were enrolled in this study. Each patient received RC48 injection [2.0 mg/kg, Q2W, iv] and Toripalimab injection [3mg/kg, Q2W, iv] for 1~2 cycles, and radiotherapy at the second or third cycle. The total dose of bladder irradiation field was greater than 50Gy (about 30 times), and the safety monitoring of the subjects was conducted within 28 days after receiving the study drug treatment for the first time. Adverse events were graded using the National Cancer Institute (NCI) Standard for the Assessment of Common Terminology for Adverse Events (CTCAE) Version 5.0 guidelines, and the occurrence of DLT in patients was observed. If the subject does not complete the safety assessment for the tolerance observation period for non-dose tolerance reasons, a new subject will be replaced.


Description:

This is a prospective, open, single-center clinical study of RC48 in combination with PD-1 and radiotherapy as bladder-preserving therapy in patients with muscular invasive bladder uroepithelial carcinoma with high HER-2 expression (IHC 2+ or 3+). The study was conducted in accordance with the Good Practice for Clinical Trials of Pharmaceutical Products (GCP). Subjects undergo maximum transurethral electrocystotomy (TURBT) or partial cystectomy, imaging diagnosis, and pre-treatment biological samples of blood, urine, and biopsy tissue. The researchers determined that localized invasive bladder cancer with high HER-2 expression could be treated with bladder conserving therapy with maximum TURBT. Patients will receive RC48 combined with PD-1 and radiotherapy after TURBT surgery. Subjects should receive RC48 combined with PD-1 every two weeks for 12 treatment cycles and radiotherapy (bladder irradiation field greater than 50Gy). After completion of the above treatment, tumor site pathology, imaging, and exfoliation cytology are obtained with diagnostic TURBT for tumor evaluation to determine complete remission, and the first tumor efficacy evaluation is performed after completion of radiotherapy (12 weeks after treatment) and every 12 weeks after completion of radiotherapy. Patients with radiotherapy intolerance (as assessed by the investigator) were discontinued directly. Adverse events will be monitored during the study period and graded using the National Cancer Institute's (NCI) Standards for the Assessment of Adverse Events in General Terminology (CTCAE) Version 5.0 guidelines. The safety assessment was carried out after 28 days. Subjects who discontinue medication for reasons other than disease progression will be followed for post-treatment disease status until subjects begin other antitumor therapy, develop disease progression, withdraw informed consent, die, or end of the study, whichever occurs first. All subjects will be followed up via outpatient cystoscopy (every 3 months within 1 year of withdrawal and every 6 months after 1 year) until subject's death, withdrawal of informed consent, or the end of the study, whichever occurs first. Participation in this study will require participants to submit a TURBT tumor tissue specimen or a newly obtained tumor lesion biopsy from prior untreated radiation therapy for biomarker and efficacy correlation evaluation. Blood and urine samples from patients will be collected during the treatment to explore potential biomarkers correlated to the treatment efficacy and patient response.


Recruitment information / eligibility

Status Recruiting
Enrollment 6
Est. completion date February 13, 2024
Est. primary completion date December 13, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion criteria: ECOG PS: 0~1;Subjects underwent TURBT surgery or partial cystectomy and imaging diagnosis, which was determined to be muscular infiltrating urothelial carcinoma of the bladder (urothelial carcinoma being the main pathological component: 50%) and planned to undergo radical total cystectomy + lymph node dissection + urine flow diversion; cT2-T4a N0 M0 (CT/MRI ± PET/CT);Undergo TURBT or partial cystectomy;Tissue examination specimens with TURBT or partial cystectomy;Expected survival =3 months;Immunohistochemical staining of tissue after final TURBT or partial cystectomy showed IHC 2+ or 3+;The major organs are functioning normally, the following criteria are met: 1. The blood routine examination criteria should meet (no blood transfusion and no treatment with granulocyte colony stimulating factor within 14 days before enrollment) : i. Absolute count of neutrophils (ANC) =1,000/mm3 ii. Platelet count =75,000/mm3 iii. Hemoglobin = 8.0g /dL 2. Liver function: i. Total bilirubin =1.5× prescribed ULN or direct bilirubin =ULN for subjects with total bilirubin levels >1.5×ULN ii. Upper limit of normal values (ULN) =2.5 times of alanine Aminotransferase (ALT) and aspartate Aminotransferase (AST) Note: =1.5× ULN (This criterion only applies to patients who have not received anticoagulant therapy; Patients receiving anticoagulant therapy should keep anticoagulants within therapeutic limits); 3. Kidney function: The Cockcroft-Gault formula was used to determine the creatinine clearance (CrCl) > 30 mL/min. Subjects (or their legal representatives) must sign an informed consent form (ICF) indicating that they understand the purpose and procedures of the study and are willing to participate in the study; Fertile women must have a negative pregnancy test result (beta-hCG) (urine or serum) within 7 days before the study drug is first administered. Exclusion criteria: Previously received anti-PD-1, anti-PD-L1, anti-PD-L2 therapy, including adjuvant therapy stage;Known allergy to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components;Those who had received other antitumor therapy (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks prior to study therapy, or had not recovered from previous toxicity (except for 2 degree hair loss and 1 degree neurotoxicity);Pregnant or lactating woman;HIV positive;People with active hepatitis B or C;A history of definite active tuberculosis;Have active autoimmune diseases requiring systemic treatment within the past 2 years (e.g., use of disease-regulating drugs, corticosteroids, or immunosuppressive drugs) that allow for relevant replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for renal or pituitary insufficiency);Other serious, uncontrolled concomitant diseases that may affect protocol adherence or interfere with interpretation of results, These include active opportunistic or progressive (severe) infections, uncontrolled diabetes, cardiovascular disease (heart failure of Grade ? or ? as defined by the New York Heart Association scale, heart block of degree ? or higher, myocardial infarction within the past 6 months, unstable arrhythmia or unstable angina, cerebral infarction within 3 months, etc.), or pulmonary disease (interstitial pneumonia, History of obstructive pulmonary disease and symptomatic bronchospasm);Those who received the live vaccine within 4 weeks before treatment began;Previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;Major surgical procedures (excluding diagnostic surgery) within 4 weeks prior to the start of treatment;Those who have a history of psychotropic substance abuse and cannot abstain or have a history of mental disorders;A large amount of pleural fluid or ascites with clinical symptoms or symptomatic management;Have had other unhealed malignancies in the past 5 years, excluding those that are apparently cured or curable, such as basal or squamous cell skin cancer, localized low-risk prostate cancer, carcinoma in situ of the cervix or carcinoma in situ of the breast; Remarks: Patients with localized low-risk prostate cancer (defined as stage =T2b, Gleason score =7, and PSA=20ng/mL at the time of prostate cancer diagnosis (as measured) who had received radical therapy and had no biochemical recurrence of prostate specific antigen (PSA) were eligible to participate in this study);Urothelial carcinoma associated with upper urinary tract (renal pelvis and ureteral urothelial carcinoma);Other severe, acute, or chronic medical or psychiatric conditions or laboratory abnormalities that, according to the investigator, may increase the risks associated with study participation or may interfere with the interpretation of the study results

Study Design


Intervention

Drug:
Disitamab Vedotin and Toripalimab
Each patient received RC48 injection [2.0 mg/kg, Q2W, iv] and Toripalimab injection [3mg/kg, Q2W, iv] for 1~2 cycles, and Radiotherapy radiotherapy at the second or third cycle. The total dose of bladder irradiation field was greater than 50Gy (about 30 times), and the safety monitoring of the subjects was conducted within 28 days after receiving the study drug treatment for the first time.

Locations

Country Name City State
China Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Shanghai

Sponsors (1)

Lead Sponsor Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety Adverse events will be defined according to NCI CTCAE, Version 5.0 Up to 28 days
Secondary Percent of Patients With Complete Response (CR) CR is defined by negative cystoscopy, urine cytology, and bladder biopsies. Up to 3 months
Secondary Percent of Patients With Complete Response (CR) CR is defined by negative cystoscopy, urine cytology, and bladder biopsies. Up to 12 months
Secondary Percent of Patients With Complete Response (CR) CR is defined by negative cystoscopy, urine cytology, and bladder biopsies. Up to 24 months
Secondary 1-yr and 2-yr Bladder-intact Event-free Survival (BI-EFS) Defined by time from enrollment to the occurrence of one of the following events: disease progression, switch to other therapy, intolerant adverse events, or death Up to 24 months
Secondary Recurrence Free Survival (RFS) Defined by time from day of first treatment to recurrent NMIBC based on cystoscopy, cytology and/or biopsy. Up to 24 months
Secondary Overall Survival (OS) Defined by time from day of first treatment to death Up to 24 months
Secondary Cancer-Specific Survival Defined by time from day of first treatment to metastatic bladder cancer Up to 24 months
See also
  Status Clinical Trial Phase
Recruiting NCT03212742 - Phase I/IIa Study of Concomitant Radiotherapy With Olaparib and Temozolomide in Unresectable High Grade Gliomas Patients Phase 1/Phase 2
Recruiting NCT06190782 - Local Therapy for Oligometastatic ESCC Patients Treated With PD-1 Inhibitor Phase 3
Recruiting NCT06120127 - Postoperative Chemotherapy With/Without Radiotherapy and Immunotherapy for Colorectal Liver Metastases With High Risk of Locally Recurrence Phase 2
Recruiting NCT05176002 - Camrelizumab in Combination With Radiotherapy for Neoadjuvant Esophageal Carcinoma. Phase 1/Phase 2
Not yet recruiting NCT05909137 - Omitting Clinical Target Volume in Radical Treatment of Unresectable Stage III Non-small Cell Lung Cancer
Recruiting NCT02661152 - DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC. Phase 3
Withdrawn NCT02542137 - Abscopal Effect for Metastatic Small Cell Lung Cancer Phase 2
Completed NCT01212731 - Skull Base and Low Grade Glioma Neurocognitive Magnetic Resonance Imaging (MRI) Study
Completed NCT01168479 - FLAME: Investigate the Benefit of a Focal Lesion Ablative Microboost in Prostate Cancer Phase 3
Recruiting NCT03658343 - T2* MRI Analysis for Sarcoma N/A
Completed NCT03280719 - Whole Breast + Lymph Node Irradiation: Prone Compared to Supine Position in 15 or 5 Fractions N/A
Recruiting NCT05515796 - Multi-omics Sequencing in Neoadjuvant Immunotherapy of Gastrointestinal Tumors Phase 2
Recruiting NCT05514327 - A Study of Ultra-fraction Radiotherapy Bridging CART in R/R DLBCL N/A
Recruiting NCT04453826 - Concurrent and Adjuvant PD1 Treatment Combined With Chemo-radiotherapy for High-risk Nasopharyngeal Carcinoma Phase 3
Recruiting NCT03370926 - FET-PET and Multiparametric MRI for High-grade Glioma Patients Undergoing Radiotherapy N/A
Active, not recruiting NCT03870919 - Locoregional Treatment and Palbociclib in de Novo, Treatment Naive, Stage IV ER+, HER2- Breast Cancer Patients N/A
Active, not recruiting NCT02428049 - Radiation Pneumonitis After SBRT for NSCLC
Recruiting NCT04923620 - Neoadjuvant Cetuximab + Chemotherapy Combined With Short-course Radiotherapy
Active, not recruiting NCT05371795 - Comparison on Radiotherapy Permanent Skin Marking With Lancets and an Electric Marking Device N/A
Recruiting NCT03210428 - Quantitative MR Imaging in Locally Advanced Cervical Cancer