Primary Excision Combined With Preoperative Neoadjuvant and Adjuvant Therapy for Oligometastasis of Urothelial Carcinoma

Sponsor

The First Affiliated Hospital with Nanjing Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04570410

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

treatment of primary focal resection plus lymph node dissection combined with chemotherapy and anti-programmed cell death 1(PD-1) for Oligometastasis of urothelial carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Bladder Urothelial Carcinoma	Procedure: primary focal resection plus lymph node dissection Drug: Tislelizumab Drug: Gemcitabine plus cisplatin	Phase 2

Detailed Description

The study is designed to demonstrate that Whether the perioperative comprehensive treatment of primary focal resection plus lymph node dissection combined with chemotherapy and anti-PD-1 can prolong the overall survival of patients, narrow the range of metastatic lesions and improve the quality of life of patients.

Compared with patients with extensive metastasis, 2-year tumor-specific survival and overall survival of patients with oligometastatic bladder cancer were significantly increased (53.3% vs 16.1%)；(51.9% vs. 15.4%).Gemcitabine plus cisplatin (GC) regimen has been shown to bring clinical benefits in neoadjuvant therapy of metastatic UC（urothelial carcinoma）.

PD-1 inhibitors have been widely used in urothelial carcinoma in recent years, and positive data have been obtained in both advanced patients and neoadjuvant patients.

If successful in this trial, it will serve to provide a therapeutic alternative for this patient who have oligometastasis of urothelial carcinoma.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Trials of Primary Excision Combined With Preoperative Neoadjuvant Therapy and Adjuvant Therapy Was Used as a First-line Comprehensive Therapy for Oligometastasis of Urothelial Carcinoma（UC）.

Actual Study Start Date :

Oct 1, 2020

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subgroup1:Patients who can tolerate cisplatin chemotherapy GC plus Tislelizumab Participants receive GC (Gemcitabine plus cisplatin), in combination with Tislelizumab administered intravenously (IV) every 3 weeks (Q3W) before surgery.Immunotherapy was continued for 6 months after excision of the primary lesion. Intervention/treatment： Biological: Tislelizumab Tislelizumab IV infusion of 200 mg Q3W Biological: GC GC (Gemcitabine plus cisplatin): Gemcitabine 1000mg/m2 D1,D8 iv every 3 weeks Cisplatin70mg/m2,D2,3,4 iv every 3 weeks	Procedure: primary focal resection plus lymph node dissection Primary radical resection plus lymph node dissection was performed in patients with oligometastatic urothelial carcinoma Drug: Tislelizumab Tislelizumab IV infusion of 200 mg Q3W Other Names: PD-1 Drug: Gemcitabine plus cisplatin GC (Gemcitabine plus cisplatin): Gemcitabine 1000mg/m2 D1,D8 iv every 3 weeks Cisplatin70mg/m2,D2,3,4 iv every 3 weeks Other Names: GC
Experimental: Subgroup2:Patients who cannot tolerate cisplatin chemotherapy Tislelizumab Participants receive Tislelizumab administered intravenously (IV) every 3 weeks (Q3W) before surgery.Immunotherapy was continued for 6 months after excision of the primary lesion. Intervention/treatment： Biological: Tislelizumab Tislelizumab IV infusion of 200 mg Q3W	Procedure: primary focal resection plus lymph node dissection Primary radical resection plus lymph node dissection was performed in patients with oligometastatic urothelial carcinoma Drug: Tislelizumab Tislelizumab IV infusion of 200 mg Q3W Other Names: PD-1

Arm

Intervention/Treatment

Experimental: Subgroup1:Patients who can tolerate cisplatin chemotherapy

GC plus Tislelizumab Participants receive GC (Gemcitabine plus cisplatin), in combination with Tislelizumab administered intravenously (IV) every 3 weeks (Q3W) before surgery.Immunotherapy was continued for 6 months after excision of the primary lesion. Intervention/treatment： Biological: Tislelizumab Tislelizumab IV infusion of 200 mg Q3W Biological: GC GC (Gemcitabine plus cisplatin): Gemcitabine 1000mg/m2 D1,D8 iv every 3 weeks Cisplatin70mg/m2,D2,3,4 iv every 3 weeks

Procedure: primary focal resection plus lymph node dissection

Primary radical resection plus lymph node dissection was performed in patients with oligometastatic urothelial carcinoma

Drug: Tislelizumab

Tislelizumab IV infusion of 200 mg Q3W

Other Names:

PD-1

Drug: Gemcitabine plus cisplatin

GC (Gemcitabine plus cisplatin): Gemcitabine 1000mg/m2 D1,D8 iv every 3 weeks Cisplatin70mg/m2,D2,3,4 iv every 3 weeks

Other Names:

Experimental: Subgroup2:Patients who cannot tolerate cisplatin chemotherapy

Tislelizumab Participants receive Tislelizumab administered intravenously (IV) every 3 weeks (Q3W) before surgery.Immunotherapy was continued for 6 months after excision of the primary lesion. Intervention/treatment： Biological: Tislelizumab Tislelizumab IV infusion of 200 mg Q3W

Procedure: primary focal resection plus lymph node dissection

Primary radical resection plus lymph node dissection was performed in patients with oligometastatic urothelial carcinoma

Drug: Tislelizumab

Tislelizumab IV infusion of 200 mg Q3W

Other Names:

PD-1

Outcome Measures

Primary Outcome Measures

1 year overall survival(OS) rate [1 year]
the percentage of patients who die of any cause within first year of treatment

Secondary Outcome Measures

progression-free survival(PFS) [through study completion, an average of 1 year]
time between the first objective recording of PD(progressive disease) or death from any cause (whichever occurs first) from random group solstice

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patients with oligometastatic urothelial carcinoma, including :patients with T2-T4 with any metastasis(T4NxM1) urothelial carcinoma diagnosed by pathology and evaluated by imaging; A. a solitary metastatic organ, B. number of metastatic lesions of ≤3, C. the largest diameter of metastatic foci of ≤5cm, D. absence of liver metastasis.The researchers assessed the benefits of excision of the primary lesion.
18 to 75 years old.
Volunteer to participate in the trial, be able to provide a written informed consent, and understand and agree to comply with the study requirements and evaluation schedule.
Eastern Cooperative Oncology Group (ECOG) performance status <2
International standardized ratio or activated partial thrombin time ≤1.5 upper limit of normal value (ULN);The calculated creatinine clearance rate was ≥60ml/min;Serum total bilirubin ≤1.5×ULN;aspartate transaminase(AST), Alanine transaminase(ALT) and alkaline phosphatase ≤2.5×ULN;
Non-pregnant or fertile men or women must be willing to take effective contraceptive measures during the study period and ≥120 days after the last administration of tislelizumab, and the women should be negative on urine or serum pregnancy test results less than or equal to 7 days before enrollment.

Exclusion Criteria:

Previous therapy targeted at PD-1, PD-L1, PD-L2, Cytotoxic T-Lymphocyte Associated Protein 4(CTLA-4)or other antibodies or drugs specifically targeting T cell synergistic stimulation or checkpoint channels.
Other approved systemic anti-cancer therapies or systemic immune modulators (including but not limited to interferon, interleukin-2, and tumor necrosis factor) were received within 28 days prior to enrollment.
Severe chronic or active infections requiring systemic antimicrobial, antifungal, or antiviral therapy within 14 days prior to enrollment.
Major surgery or major trauma occurred within 28 days prior to enrollment.
Live vaccine was administered within 28 days before enrollment.
Received any herbal or proprietary Chinese medicine used to control cancer in the 14 days prior to enrollment.
Active autoimmune disease requiring long-term use of large amounts of hormones and other immunosuppressive agents.
The researchers identified abnormalities in potassium, sodium, calcium, or hypoalbuminemia, interstitial lung disease, non-infectious pneumonia, or other uncontrolled whole-body diseases, including diabetes, hypertension, and cardiovascular disease, that may affect treatment.
A history of HIV, hepatitis B virus(HBV)and hepatitis C virus(HCV) infection is known.
A history of known allergic reactions to any of the drugs studied.
Is participating in additional clinical studies.
The researcher believes that the patient is not suitable to participate in this study (such as the treatment that does not meet the patient's greatest benefit, patient compliance, etc.)