Trial Title:
Treating Muscle-invasive Bladder Cancer With A Non-surgical Method Consisting of Anti-PD-1 Therapy and Chemoradiation
NCT ID:
NCT05975307
Condition:
Muscle-Invasive Bladder Carcinoma
Programmed Cell Death Protein 1 Inhibitor
Radiotherapy
Conditions: Official terms:
Urinary Bladder Neoplasms
Carboplatin
Gemcitabine
Conditions: Keywords:
Bladder Cancer
Programmed Cell Death Protein 1 Inhibitor
Radiotherapy
Chemotherapy
Bladder Preservation
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This Phase 2 trial uses a single-arm, Simon's two-stage design.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Toripalimab
Description:
The patients in this arm will receive 3 cycles of induction treatment containing
chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones
without progressive disease will receive radical radiotherapy, plus 2 cycles of
concurrent toripalimab.
Toripalimab: 240 mg on Day 1, every 3 weeks, totally 3 and 2 cycles in the induction and
concurrent phases, respectively.
Arm group label:
Toripalimab plus chemoradiation
Other name:
JS001
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
The patients in this arm will receive 3 cycles of induction treatment containing
chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones
without progressive disease will receive radical radiotherapy, plus 2 cycles of
concurrent toripalimab.
Gemcitabine: 1 g/m2 on Days 1 and 8, repeated every 3 weeks, totally 3 cycles.
Arm group label:
Toripalimab plus chemoradiation
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
The patients in this arm will receive 3 cycles of induction treatment containing
chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones
without progressive disease will receive radical radiotherapy, plus 2 cycles of
concurrent toripalimab.
Cisplatin: Used when creatinine clearance rate ≥ 40 ml/min, 37.5 mg/m2 on Days 1 and 2,
repeated every 3 weeks, totally 3 cycles.
Arm group label:
Toripalimab plus chemoradiation
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
The patients in this arm will receive 3 cycles of induction treatment containing
chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones
without progressive disease will receive radical radiotherapy, plus 2 cycles of
concurrent toripalimab.
Cisplatin: Used when creatinine clearance rate < 40 ml/min, area under curve = 2 on Days
1 and 2, repeated every 3 weeks, totally 3 cycles.
Arm group label:
Toripalimab plus chemoradiation
Intervention type:
Radiation
Intervention name:
Intensity-modulated radiation therapy
Description:
The patients in this arm will receive 3 cycles of induction treatment containing
chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones
without progressive disease will receive radical radiotherapy, plus 2 cycles of
concurrent toripalimab.
Radiotherapy: performed by using the technique of intensity-modulated radiation therapy,
with a total dose of 65 and 45 Gy for the gross tumor and lymphatic drainage regions.
Arm group label:
Toripalimab plus chemoradiation
Summary:
The goal of this Phase 2 trial is to evaluate a non-surgical bladder-preserving treatment
mode which consists of induction chemotherapy plus anti-programmed cell death protein 1
(anti-PD-1) therapy followed by radiotherapy plus concurrent anti-PD-1 therapy. The main
questions it aims to answer are: (i) whether the anti-PD-1 antibody, toripalimab, is
effective in treating muscle-invasive bladder cancer (MIBC), when combined with
chemoradiation; (ii) whether toripalimab is safe in combination with chemoradiation.
Participants will receive 3 cycles of induction treatment containing chemotherapy with
gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without
progressive disease will receive radical radiotherapy plus 2 cycles of concurrent
toripalimab.
Detailed description:
Bladder cancer is the second most common malignancies over the world. At initial
diagnosis, the cases with muscle-invasive bladder cancer (MIBC) accounts nearly 20% of
all bladder cancer patients. And 40% of non-muscle-invasive bladder cancer could develop
to MIBC. Currently, radical cystectomy (RC) is the golden standard to manage MIBC. Yet,
it brings severe surgical injuries and post-surgical complications which impair life
quality of the patients. Recently, bladder-preserving treatment based gradually becomes
the second choice for MIBC. It consists of maximal transurethral resection of bladder
tumor (TURBT) and chemoradiation. A series of clinical trials and meta-analyses supported
that the bladder-preserving treatment has a similar therapeutic effect compared with RC.
But it is noteworthy that this treatment mode does not really avoid surgery. TURBT could
also cause complications, such as haemorrhage, infection, perforation, and even tumor
dissemination. Moreover, the incidence of serious toxicities brought by concurrent
chemoradiation is as high as 36%. In actual clinical work, it is hard for more than half
patients to complete chemoradiation of standard intensity. Additionally, many patients
are unsuitable for bladder preservation, including those with T stage > T2, diameter > 5
cm, hydronephrosis and positive lymph nodes. Hence, it calls for improvement of current
bladder preservation mode, to make more MIBC patients receive radical treatment which
brings better therapeutic experience and life quality.
Many lab studies indicated that formation and progression of bladder cancer is a process
of mutation accumulation. It provides biological fundamentals for immune checkpoint
inhibitors, such as anti-programmed cell death protein 1 (anti-PD-1) antibodies. Based on
available clinical studies, anti-PD-1 antibodies exhibits ideal therapeutic effects in
bladder cancer of different stages and has an incidence of toxicities as low as 13%. Its
toxicities mainly include arthralgia and hyponatremia, which are well tolerated.
Currently, there are more than 10 clinical trials trying anti-PD-1 antibodies for bladder
preservation. However, the treatment modes in most of them still contain TURBT. This
phase 2 trial intended to evaluate the therapeutic and adverse effects of a non-surgical
bladder-preserving treatment mode consisting of anti-PD-1 antibodies and chemoradiation,
in a small patient cohort with MIBC. The results might provide an effective, non-invasive
and low-toxic choice which improves patient experience and realizes bladder preservation.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Pathologically diagnosed bladder malignant tumor via biopsy
- Urothelial carcinoma as the primary histological component
- Pretreatment clinical TNM stage as T2-4aN0M0 or T1-4aN1-2M0 (UICC TNM staging
classification, version 8)
- Age between 18 and 75 years old
- Karnofsky performance score ≥ 70
- Creatinine clearance rate ≥ 30 ml/min
Exclusion Criteria:
- Simultaneous tumors of the urethra or upper urinary tract
- Existence of small cell cancer component
- Uncontrolled tuberculosis, viral hepatitis or AIDS
- Autoimmune or mental diseases
- Severe cardiac, renal, hepatic or hematopoietic dysfunctions unsuitable for
chemotherapy, radiotherapy or immune checkpoint inhibiting therapy
- Prior history of other malignancies within 5 years, except cured cervical carcinoma
in situ and skin basal cell carcinoma
- Prior history of pelvic radiotherapy or chemotherapy
- Poor adherence to regular follow-up (cystoscopy, CT, MRI, etc.)
- Pregnant or lactating women
- Treatment with glucocorticoid or immunosuppressive drugs within 1 month
- Other situations for which the investigators consider a patient inappropriate to
participate
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Center, Sun Yat-sen University
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Hui Chang, MD
Phone:
+86-020-87343374
Email:
changhui@sysucc.org.cn
Start date:
December 1, 2023
Completion date:
December 31, 2029
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05975307
