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

NCT04706598 | Active Not Recruiting Phase 1

• 1 other identifier: MA-UC-II-004
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Urinary Bladder Neoplasms; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• The maximum dose of Camrelizumab for intravesical treatment

  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)

  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 Outcomes (5)

• Incidence of adverse events

  Until progressive disease or death

• Assessment of HGRF

  6 months and 1 year after patient enrollment

• Assessment of RFS

  6 months and 1 year after patient enrollment

• Assessment of PFS

  6 months and 1 year after patient enrollment

• the predictive value of PD-1 expresssion

  1 year after patient enrollment

Study Arms (1)

Intravesical therapy group

EXPERIMENTAL

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

Interventions

Camrelizumab DRUG

Solution for Infusion (Intravesical)

Also known as: SHR-1210

Intravesical therapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• 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%).
• Fully resected disease at study entry (residual CIS acceptable).
• 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).
• Ineligible for radical cystectomy or refusal of radical cystectomy.
• Consent to tissue specimen retrieval and testing.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin (HB) ≥ 90 g/L
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L(no granulocyte colony-stimulating factor support for 2 weeks before day 1 of cycle 1)
• Lymphocyte count≥0.500×10\^9/L
• Platelet count ≥100×10\^9/L(No blood transfusions within 2 weeks before day 1 of cycle 1)
• ×10\^9/L≤White Blood Cell Count (WBC)≤15×10\^9/L
• 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)
• INR/aPTT≤1.5×ULN(Which only applies to patients not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be given a stable dose)

You may not qualify if:

• Muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma.
• Concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis)urothelial cell carcinoma.
• Have participated in a clinical trial of an investigational drug or device within 4 weeks prior to receiving the first treatment in this project.
• Received chemotherapy, targeted small molecule therapy, immunotherapy or radiation therapy following a recent cystoscopy or transurethral resection of a bladder tumour.
• History of other malignancies within the last 5 years.
• Active autoimmune disease that has required systemic treatment in the past 2 years.
• 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.
• 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).
• Patients who are pregnant or breastfeeding, or expecting to conceive .
• 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.
• Patients with known positive test for human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
• 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).
• Received a live virus vaccine within 30 days of planned start of study treatment.
• Has had an allogeneic tissue/solid organ transplant.
• Long-term oral steroids, more than 10 mg/day of methandrostenolone or similar, must be stopped for 28 days before entry into the group.

Sponsors & Collaborators

• Fudan University: lead
• Shanghai Shen Kang Hospital Development Center: collaborator

Study Sites (4)

Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200011, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai Tenth People's Hospital,Shanghai Tong Ji University School of Medicine

Shanghai, Shanghai Municipality, 200072, China

Location

Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200080, China

Location

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MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

camrelizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Xiang Wang, MD

  Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

  STUDY DIRECTOR

• Yushan Liu, MD

  Shanghai Ninth People's 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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 27, 2020
• First Posted: January 13, 2021
• Study Start: June 9, 2021
• Primary Completion: July 11, 2024
• Study Completion: December 1, 2024
• Last Updated: July 12, 2024

Record last verified: 2024-07

Locations

CN (4)