Trial Title:
RC48 Combined With Toripalimab and Radiotherapy for Bladder Sparing Treatment in MIBC
NCT ID:
NCT05979740
Condition:
Muscle Invasive Bladder Cancer
HER2 Expression
Radiotherapy
PD-1
Antibody-drug Conjugates
Conditions: Official terms:
Urinary Bladder Neoplasms
Disitamab vedotin
Conditions: Keywords:
Muscle Invasive Bladder Cancer
HER2 expression
Radiotherapy
PD-1
ADC
Bladder Sparing
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Disitamab Vedotin and Toripalimab
Description:
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.
Arm group label:
RC48+Toripalimab+Radiotherapy
Other name:
RC48, JS001
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.
Detailed 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.
Criteria for eligibility:
Criteria:
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 Ⅲ or Ⅳ as defined by the New York Heart Association scale, heart block
of degree Ⅱ 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Address:
City:
Shanghai
Zip:
200127
Country:
China
Status:
Recruiting
Contact:
Last name:
haige chen, M.D
Phone:
86-21-68383575
Email:
kirbyhaige@aliyun.com
Investigator:
Last name:
Haige Chen, M.D
Email:
Principal Investigator
Start date:
August 1, 2023
Completion date:
February 13, 2024
Lead sponsor:
Agency:
RenJi Hospital
Agency class:
Other
Source:
RenJi Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05979740
