Clinical trial NCT04861584: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Urinary Bladder Cancer
Keywords: bladder cancer
checkpoint inhibitor
neoadjuvant therapy
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
First posted: 2021-04-27
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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;

Primary outcomes:
measure: 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
timeFrame: Up to 90 days after last dose of investigation product
Secondary outcomes:
measure: Safety assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4 criteria
timeFrame: From the first day of the treatment to the end of neoadjuvant treatment, assessed up to 6 month
measure: Progression-free survival assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1
timeFrame: 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
measure: Tumor immune microenvironment indicators assessed by Microenvironment Analysis Panel
timeFrame: Assessed lasted for 24 months, calculated from the date of enrolled
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhujiang Hospital
state: Guangdong
Study officials:
affiliation: Zhujiang Hospital
name: Abai Xu, doctor
role: PRINCIPAL_INVESTIGATOR
References: