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Neoadjuvant Toripalimab in Combination With Gemcitabine and Cisplatin Therapy in Local Advanced Bladder Cancer Subjects

Primary Purpose

Urinary Bladder Cancer

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Neoadjuvant Toripalimab in Combination With Gemcitabine and Cisplatin

About this trial

This is an interventional treatment trial for Urinary Bladder Cancer focused on measuring bladder cancer, checkpoint inhibitor, neoadjuvant therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients between 18 and 75 years old on day of signing informed consent, regardless of gender;
ECOG score 0-1 points, expected survival time> 6 months;
Pathologically confirmed locally advanced bladder urothelial carcinoma (cT2-T4a, N≤1, M0, tumor staging according to American Joint Committee on Cancer (AJCC), 2017, eighth edition);
Appropriate and plan for radical cystectomy;
According to the RECIST1.1 standard, there is at least one measurable lesion (spiral CT scan ≥10mm);
Since the diagnosis of locally advanced bladder urothelial carcinoma, patient has not received anti-tumor system treatment;
The main organ functions are normal, and the following requirements must be met within 2 weeks before the first study treatment:
Routine blood examination must meet: WBC≥4.0×109/L; PLT≥90×109/L; Hb≥90g/L (patients can be infused with red blood cells to meet this standard);
Blood biochemical examination must meet: serum creatinine (Cr) ≤1.5 times the upper limit of normal (ULN) or endogenous creatinine clearance ≥60mL/min; TBIL≤1.5×ULN; ALB≥30g/L; ALT and AST≤ 3.0×ULN; TSH≤1.5×ULN.
Female patients with fertility must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and they voluntarily adopt appropriate methods of contraception during the observation period and within 8 weeks after the last administration;
Agree to provide diagnosis and treatment-related tumor tissue specimens for clinical research, and have the ability to follow the planned research visit until the clinical recurrence/progress is clear.
Sign informed consent voluntarily.

Exclusion Criteria:

Have previously received anti-PD1/PDL1/CTLA-4 antibody treatment or systemic chemotherapy, bladder infusion chemotherapy is excluded;
Have received bladder bacille Calmette Guerin (BCG) infusion therapy within 4 weeks;
Have received radiotherapy of the bladder in the past;
Patients with any history of active autoimmune disease or autoimmune disease;
Complicated diseases that require the use of immunosuppressive drugs; concurrent diseases that require the use of immunosuppressive agents for systemic or locally absorbable corticosteroids. It is forbidden to use prednisone greater than 10 mg/day or the same dose in the 2 weeks before the use of the study drug;
Combined with other malignant tumors;
Have a history of allergy to other antibody drugs;
The history of human immunodeficiency virus (HIV) infection;
The subject has active infection, including active tuberculosis;
Combined with severe heart disease, or combined with New York Heart Association (NYHA) grade 3 or 4 cardiac insufficiency;
Kidney transplant patients;

Sites / Locations

Zhujiang HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Toripalimab+Gemcitabine/Cisplantin（GC）

Arm Description

Subjects receive gemcitabine/cisplatin every 21 days, repeated for 4 cycles. . Toripalimab is given every 21 days for 4 doses starting C1D1. Subjects will then have consolidative surgery to remove their primary tumor within 6 weeks after their last dose of neoadjuvant therapy.

Outcomes

Primary Outcome Measures

Pathological response rate evaluated after 4 cycles of neoadjuvant Toripalimab in combination with gemcitabine and cisplatin at time of radical cystectomy, each cycle is 21 days

the absence of residual muscle invasive bladder cancer in surgical specimens of cystectomy (pathologically decreased to ≤pT1N0, including pT0, pT1, pTa and pTis

Secondary Outcome Measures

Safety assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4 criteria

To assess safety of Toripalimab in combination with gemcitabine and cisplatin in patients with bladder cancer according to CTCAE v4 criteria

Progression-free survival assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1

From the start of neoadjuvant therapy to the time when any disease progression is first recorded, disease progression includes the progression detected by clinical or imaging before cystectomy, as well as the distant metastasis or pelvic recurrence after cystectomy. Newly discovered primary tumors in other parts of the urinary tract such as renal pelvis, ureter and urethra are not considered as disease progression.

Tumor immune microenvironment indicators assessed by Microenvironment Analysis Panel

The expression rate of PDL1 in pathological specimens assessed by Burning Rock's product OncoScreen plus+Microenvironment Analysis Panel at the time of surgery

Full Information

NCT ID

NCT04861584

First Posted

April 9, 2021

Last Updated

January 6, 2023

Sponsor

Zhujiang Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04861584

Brief Title

Neoadjuvant Toripalimab in Combination With Gemcitabine and Cisplatin Therapy in Local Advanced Bladder Cancer Subjects

Official Title

Phase II Study of Neoadjuvant Toripalimab With Gemcitabine-Cisplatin in Subjects With T2-4aN0M0 Bladder Cancer: GZZJU-2021NB

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 3, 2021 (Actual)

Primary Completion Date

October 3, 2023 (Anticipated)

Study Completion Date

April 3, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Zhujiang Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a pre-surgical study involving subjects with local advanced bladder cancer, who are candidates for neoadjuvant therapy. It is a single-arm phase II portion.

Detailed Description

Outline: This study is a single-arm, open, exploratory clinical trial; Subjects receive: gemcitabine 1000mg/m2 IV Day1 and Day8 every 21 days repeated for 4 cycles; cisplatin 35mg/m2 IV Day1 and Day2 every 21 days, repeated for 4 cycles. Toripalimab at recommended phase II dose is given every 3 weeks for 4 doses starting with Cycle1 Day1(C1D1). Subjects will then have surgery to remove their primary tumor within 6 weeks after their last dose of neoadjuvant therapy. Eastern Cooperative Oncology Group (ECOG) performance status: 0-1 Demonstrate adequate organ function as defined by the following laboratory values at study entry. All screening labs should be performed within 28 days of C1D1. Hematopoetic: Absolute neutrophil count (ANC) ≥1,500 /mcL Absolute lymphocyte count ≥350 mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L Renal: Measured or calculated creatinine clearance ≥30 mL/min Hepatic: Serum total bilirubin ≤ 1.25 X ULN OR ≤ 2.5 x ULN for subjects with Gilbert's disease Aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT) ≤ 2 X ULN Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy and as long as PT or PTT is within therapeutic range of intended use of anticoagulants

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Urinary Bladder Cancer

Keywords

bladder cancer, checkpoint inhibitor, neoadjuvant therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Toripalimab+Gemcitabine/Cisplantin（GC）

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Neoadjuvant Toripalimab in Combination With Gemcitabine and Cisplatin

Other Intervention Name(s)

Toripalimab

Intervention Description

4 cycle neoadjuvant therapy and radical cystectomy

Primary Outcome Measure Information:

Title

Pathological response rate evaluated after 4 cycles of neoadjuvant Toripalimab in combination with gemcitabine and cisplatin at time of radical cystectomy, each cycle is 21 days

Description

the absence of residual muscle invasive bladder cancer in surgical specimens of cystectomy (pathologically decreased to ≤pT1N0, including pT0, pT1, pTa and pTis

Time Frame

Up to 90 days after last dose of investigation product

Secondary Outcome Measure Information:

Title

Safety assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4 criteria

Description

To assess safety of Toripalimab in combination with gemcitabine and cisplatin in patients with bladder cancer according to CTCAE v4 criteria

Time Frame

From the first day of the treatment to the end of neoadjuvant treatment, assessed up to 6 month

Title

Progression-free survival assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1

Description

Time Frame

From the start of neoadjuvant therapy to the time when any disease progression is first recorded. Assessed lasted for 24 months, calculated from the date of enrolled

Title

Tumor immune microenvironment indicators assessed by Microenvironment Analysis Panel

Description

The expression rate of PDL1 in pathological specimens assessed by Burning Rock's product OncoScreen plus+Microenvironment Analysis Panel at the time of surgery

Time Frame

Assessed lasted for 24 months, calculated from the date of enrolled

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients between 18 and 75 years old on day of signing informed consent, regardless of gender; ECOG score 0-1 points, expected survival time> 6 months; Pathologically confirmed locally advanced bladder urothelial carcinoma (cT2-T4a, N≤1, M0, tumor staging according to American Joint Committee on Cancer (AJCC), 2017, eighth edition); Appropriate and plan for radical cystectomy; According to the RECIST1.1 standard, there is at least one measurable lesion (spiral CT scan ≥10mm); Since the diagnosis of locally advanced bladder urothelial carcinoma, patient has not received anti-tumor system treatment; The main organ functions are normal, and the following requirements must be met within 2 weeks before the first study treatment: Routine blood examination must meet: WBC≥4.0×109/L; PLT≥90×109/L; Hb≥90g/L (patients can be infused with red blood cells to meet this standard); Blood biochemical examination must meet: serum creatinine (Cr) ≤1.5 times the upper limit of normal (ULN) or endogenous creatinine clearance ≥60mL/min; TBIL≤1.5×ULN; ALB≥30g/L; ALT and AST≤ 3.0×ULN; TSH≤1.5×ULN. Female patients with fertility must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and they voluntarily adopt appropriate methods of contraception during the observation period and within 8 weeks after the last administration; Agree to provide diagnosis and treatment-related tumor tissue specimens for clinical research, and have the ability to follow the planned research visit until the clinical recurrence/progress is clear. Sign informed consent voluntarily. Exclusion Criteria: Have previously received anti-PD1/PDL1/CTLA-4 antibody treatment or systemic chemotherapy, bladder infusion chemotherapy is excluded; Have received bladder bacille Calmette Guerin (BCG) infusion therapy within 4 weeks; Have received radiotherapy of the bladder in the past; Patients with any history of active autoimmune disease or autoimmune disease; Complicated diseases that require the use of immunosuppressive drugs; concurrent diseases that require the use of immunosuppressive agents for systemic or locally absorbable corticosteroids. It is forbidden to use prednisone greater than 10 mg/day or the same dose in the 2 weeks before the use of the study drug; Combined with other malignant tumors; Have a history of allergy to other antibody drugs; The history of human immunodeficiency virus (HIV) infection; The subject has active infection, including active tuberculosis; Combined with severe heart disease, or combined with New York Heart Association (NYHA) grade 3 or 4 cardiac insufficiency; Kidney transplant patients;

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Abai Xu, doctor

Phone

+86 18665626790

lc96xab@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Peng Xu Xu, doctor

Phone

+86 18665073650

yihuixp88@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Abai Xu, doctor

Organizational Affiliation

Zhujiang Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Zhujiang Hospital

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510282

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Peng Xu

12. IPD Sharing Statement

Learn more about this trial

Neoadjuvant Toripalimab in Combination With Gemcitabine and Cisplatin Therapy in Local Advanced Bladder Cancer Subjects

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