Safety and Efficacy of Camrelizumab for High-risk NMIBC Failing BCG Treatment

December 28, 2023 updated by: Ding-Wei Ye, Fudan University

A Phase I/II Single Arm Study of Intravesical Administration With Camrelizumab for High-risk Non-muscle Invasive Bladder Cancer(NMIBC) Failing in BCG Treatment

This study will evaluate the safety and efficacy of bladder intravesical Camrelizumab in patients with high-risk non-muscle-invasive bladder cancer who failed BCG therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Dingwei Ye, MD
  • Phone Number: +86-64175590-82800
  • Email: dwyeli@163.com

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
      • Shanghai, Shanghai, China, 200011
        • Recruiting
        • Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine
        • Contact:
          • Yushan Liu, MD
      • Shanghai, Shanghai, China, 200072
        • Recruiting
        • Shanghai Tenth People's Hospital,Shanghai Tong Ji University School of Medicine
        • Contact:
          • Xudong Yao, MD
      • Shanghai, Shanghai, China, 200080
        • Recruiting
        • Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine
        • Contact:
          • Xiang Wang, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Histologically-confirmed diagnosis of high risk non-muscle-invasive urothelial cell carcinoma of the bladder (mixed histology tumors allowed if urothelial carcinoma histology is >50%).
  3. Fully resected disease at study entry (residual CIS acceptable).
  4. BCG-unresponsive high risk non-muscle-invasive bladder cancer after treatment with adequate BCG therapy(at least five times a week during the induction phase and at least two times a week during the maintenance phase).
  5. Ineligible for radical cystectomy or refusal of radical cystectomy.
  6. Consent to tissue specimen retrieval and testing.
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  8. Adequate normal organ and marrow function as defined below:

    1. Haemoglobin (HB) ≥ 90 g/L
    2. Absolute neutrophil count (ANC) ≥1.5×10^9/L(no granulocyte colony-stimulating factor support for 2 weeks before day 1 of cycle 1)
    3. Lymphocyte count≥0.500×10^9/L
    4. Platelet count ≥100×10^9/L(No blood transfusions within 2 weeks before day 1 of cycle 1)
    5. 4.0×10^9/L≤White Blood Cell Count (WBC)≤15×10^9/L
    6. AST (SGOT)/ALT (SGPT)/Alkaline phosphatase ≤ 2.5 x institutional upper limit of normal(ULN) (excluded Gilbert's disease patients, whose serum bilirubin level ≤ 3x ULN)
    7. INR/aPTT≤1.5×ULN(Which only applies to patients not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be given a stable dose)
    8. Serum creatinine (Cr) ≤ 1.5 times the upper institutional limit of normal (ULN) or Serum creatinine Cl>60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976)
  9. Women of childbearing potential who have a negative serum pregnancy test within 72 hours prior to the first dose should consent to and must use effective contraception during and for 6 months after the end of the study.
  10. Men should consent to patients who must use contraception during the study and for 6 months after the end of the study period.
  11. The subject is personally willing and able to provide written informed consent to be able to comply with the protocol.

Exclusion Criteria:

  1. Muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma.
  2. Concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis)urothelial cell carcinoma.
  3. Have participated in a clinical trial of an investigational drug or device within 4 weeks prior to receiving the first treatment in this project.
  4. Received chemotherapy, targeted small molecule therapy, immunotherapy or radiation therapy following a recent cystoscopy or transurethral resection of a bladder tumour.
  5. History of other malignancies within the last 5 years.
  6. Active autoimmune disease that has required systemic treatment in the past 2 years.
  7. History of idiopathic pulmonary fibrosis (including pneumonia), drug-induced pneumonia, histoplasmosis (i.e. occlusive bronchiolitis, cryptogenic histoplasmosis), or evidence of active pneumonia on chest CT scan (history of fibrosis in radiation pneumonia), patients with active tuberculosis.
  8. Active infection requiring systemic therapy,therapeutic oral or intravenous (IV) antibiotics within 14 days prior to enrolment (patients receiving prophylactic antibiotics (e.g. for the prevention of urinary tract infections or chronic obstructive pulmonary disease) can be enrolled).
  9. Patients who are pregnant or breastfeeding, or expecting to conceive .
  10. Previous treatment with anti-PD-1 monoclonal antibody, PD-L1 monoclonal antibody, CTLA-4 monoclonal antibody, or other drugs that act on T-cell co-stimulation or any other antibody of the checkpoint pathway.
  11. Patients with known positive test for human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
  12. Patients with known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (Hepatitis B reference: HBsAg positive and HBV DNA ≥ 500 IU/ml; Hepatitis C reference: HCV antibody positive and HCV viral copy number > upper limit of normal value).
  13. Received a live virus vaccine within 30 days of planned start of study treatment.
  14. Has had an allogeneic tissue/solid organ transplant.
  15. Long-term oral steroids, more than 10 mg/day of methandrostenolone or similar, must be stopped for 28 days before entry into the group.
  16. Evidence of apparently uncontrolled concomitant disease that may affect compliance with the protocol or interpretation of the results, including significant liver disease (e.g. cirrhosis, uncontrolled major seizures or superior vena cava syndrome).
  17. Significant cardiovascular disease, such as New York Heart Association heart attack (class II or higher), myocardial infarction, unstable arrhythmia or unstable angina within 3 months prior to study entry.
  18. Patients who have had major surgery within 4 weeks prior to study entry, or who are expected to require major surgery during the course of the study, except diagnostic procedures such as TURBT or biopsy.
  19. History of autoimmune diseases, including but not limited to severe muscle weakness, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, angio-thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, dry syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  20. History of severe allergy, sensitisation or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins.
  21. Patients who, in the opinion of the investigator, are otherwise unable to participate in this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intravesical therapy group

Camrelizumab(SHR-1210) is administered on the first day of each treatment cycle (D1) at a dose up to 200 mg. The recommended phase II dose(RP2D) to be decided after safety run-in.

The cycle is divided into an induction course and a maintenance course. The induction course is initiated 2 weeks after TURBT and repeat once a week for 6 weeks . After that, the maintenance course starts every 3 weeks. The maximum duration of dosing is 2 years.
Drug: Camrelizumab
Solution for Infusion (Intravesical)
Other Names:
  • SHR-1210

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The maximum dose of Camrelizumab for intravesical treatment
Time Frame: 3 months after trial initiation(Phase I)
The maximum tolerated dose (MTD) of Camrelizumab that will be given intravesically to patients with BCG-refractory NMIBC(de-escalated doses of 200/150/100mg) and recommended for phase II studies (RP2D).
3 months after trial initiation(Phase I)
Event-Free Survival (EFS)
Time Frame: 3 months after patient treatment (Phase II)
Recurrence of high-grade cancer (TaHG, T1HG, CIS), or disease progression to stage T2 or beyond or lymph node metastasis or distant metastasis, or the need for other treatment (including systemic chemotherapy, radical cystectomy, radiation therapy), and death from any cause.
3 months after patient treatment (Phase II)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of HGRF
Time Frame: 6 months and 1 year after patient enrollment
High grade cancer recurrence free rate (HGFR) at 6 months and 1 year of treatment.
6 months and 1 year after patient enrollment
Assessment of RFS
Time Frame: 6 months and 1 year after patient enrollment
Recurrence free survival (RFS) at 6 months and 1 year of treatment.
6 months and 1 year after patient enrollment
Assessment of PFS
Time Frame: 6 months and 1 year after patient enrollment
Progression free survival (PFS) at 6 months and 1 year of treatment.
6 months and 1 year after patient enrollment
the predictive value of PD-1 expresssion
Time Frame: 1 year after patient enrollment
the predictive value of PD-L1 expression assessed in tumor tissue and urine sample obtained before and after Camrelizumab instillation.
1 year after patient enrollment
Incidence of adverse events
Time Frame: Until progressive disease or death
Incidence of adverse events and treatment-related adverse events
Until progressive disease or death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Collaborators

Shanghai Shen Kang Hospital Development Center

Investigators

  • Study Director: Xiang Wang, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
  • Study Director: Xudong Yao, MD, Shanghai Tenth People's Hospital,Shanghai Tong Ji University School of Medicine
  • Study Director: Yushan Liu, MD, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 9, 2021

Primary Completion (Estimated)

February 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

December 27, 2020

First Submitted That Met QC Criteria

January 10, 2021

First Posted (Actual)

January 13, 2021

Study Record Updates

Last Update Posted (Estimated)

January 1, 2024

Last Update Submitted That Met QC Criteria

December 28, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MA-UC-II-004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Urinary Bladder Neoplasms

Clinical Trials on Camrelizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe