A Phase II Study to Evaluate the Efficacy and Safety of Toripalimab Plus Nab-Paclitaxel With or Without Cisplatin as First-line Treatment of Unresectable Locally Advanced or Metastatic Urothelial Carcinoma

Jun Guo1 site in 1 country30 target enrollmentNovember 30, 2020

ConditionsUrothelial Carcinoma

InterventionsToripalimab plus Nab-Paclitaxel +/- cisplatin

DrugsToripalimab plus Nab-Paclitaxel +/- cisplatin

Overview

Phase: Phase 2
Intervention: Toripalimab plus Nab-Paclitaxel +/- cisplatin
Conditions: Urothelial Carcinoma
Sponsor: Jun Guo
Enrollment: 30
Locations: 1
Primary Endpoint: Objective response rate (ORR) by RECIST 1.1
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-center, open-label，phase II study designed to evaluate the efficacy and safety of Toripalimab plus nab-paclitaxel with or without cisplatin as first-line treatment of unresectable locally advanced or metastatic urothelial carcinoma.Each enrolled Patient will receive Toripalimab plus nab-paclitaxel with or without cisplatin until progressive disease or intolerable toxicity occurs, then enter a survival follow-up period. Nab-paclitaxel with or without cisplatin will be administered for up to 6 cycles, and Toripalimab up to 2 years.

Detailed Description

Unresectable locally advanced or metastatic urothelial carcinoma

Registry

clinicaltrials.gov

Start Date

November 30, 2020

End Date

January 30, 2023

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Jun Guo

Responsible Party

Sponsor Investigator

Principal Investigator

Jun Guo

Director

Peking University Cancer Hospital & Institute

Eligibility Criteria

Inclusion Criteria

•Fully understand the study and are willing to sign informed consent form (ICF);
•Age of ≥ 18 years at screening, male or female;
•Histopathologically confirmed locally advanced (T4b, any N; or any T, N2-3) or metastatic (M1, stage IV) unresectable bladder urothelial carcinoma (including renal pelvis, ureter, bladder, urinary tract);
•Not previously treated with systemic chemotherapy; Patients with urothelial carcinoma who have received prior adjuvant or neoadjuvant treatment or radiochemotherapy are eligible, provided that progression has occurred \>6 months from last therapy (for radiochemotherapy and adjuvant treatment) or \>6 months from last surgery (for neoadjuvant treatment).
•At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
•Providing tissue specimen for PD-L1 testing and related pathological report prior to enrollment for biomarker evaluation (tumor tissue specimen must be freshly obtained or archived within 3 months prior to enrollment; the fresh tissue must be a biopsy specimen of hollow needle punctured, excisedor resected);
•ECOG performance status score of 0 or 1;
•Life expectancy ≥ 12 weeks in the Investigator's opinion;
•Adequate organ function:
•Hematology: absolute neutrophil count (ANC) ≥1.5×109/L; platelet count ≥100×109/L; hemoglobin ≥90g/L Renal: serum creatinine level ≤1.5 × ULN; urine protein ≤ 1+, if urine protein \> 1 +, collect 24-hour urine protein determination, and the total amount should be ≤ 1 g,Liver: total bilirubin ≤ 1.5 × ULN; AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN; for patients with liver metastases, ALT and AST ≤ 5 × ULN Endocrine system: thyroid stimulating hormone (TSH) within normal range. Note: if the TSH is not within normal range at baseline, and T3 and free T4 are within normal range, the subject can still meet the inclusion criteria.

Exclusion Criteria

•Prior exposure to immune-mediated therapy (with the exclusion of Bacillus Calmette Guerin, BCG), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines;
•Currently participating in or having participated in another clinical study within 4 weeks prior to enrollment, unless it is an observational (non-interventional) clinical study;
•Radiotherapy affect more than 30% of the bone marrow or extensive radiotherapy within 4 weeks prior to enrollment;
•Major surgery within 4 weeks prior to enrollment;
•Use of any live vaccines within 4 weeks before enrollment. Including but not limited to the following:mumps, rubella, measles, varicella/ herpes zoster (chicken pox), yellow fever, Rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine (inactivated virus vaccine allowed);
•Treatment with immunosuppressive medications within 14 days prior to enrollment. The following are exceptions to this criterion:
•Intranasal, intraocular local steroids, or local steroid injections (eg, intraarticular injection) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent Steroids as preventive medication for hypersensitivity reactions (eg, CT scan premedication)
•Use of antineoplastic chemotherapy, biotherapy, hormone therapy or traditional herbal medicine t within 4 weeks prior to enrollment, except for the following:
•Concomitant medication of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable; Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable (eg, local radiotherapy or surgery);
•History of (non-infectious) pneumonia/interstitial lung disease requiring steroid treatment, or ongoing pneumonia/interstitial lung disease requiring steroid treatment;

Arms & Interventions

Treatment Arm

Intervention: Toripalimab plus Nab-Paclitaxel +/- cisplatin

Outcomes

Primary Outcomes

Objective response rate (ORR) by RECIST 1.1

Time Frame: Up to 2 years

ORR based on RECIST 1.1

Secondary Outcomes

To evaluate Progression-free Survival (PFS) assessed by the investigator based on RECIST 1.1 criteria.(Up to 2 years)
To evaluate Time to Response (TTR) assessed by the investigator based on RECIST 1.1 criteria.(Up to 2 years)
To evaluate the correlation between biomarkers (i.e. PD-L1, etc) and clinical endpoint (ORR) and/or incidence of adverse event.(Up to 2 years)
To evaluate Duration of Response (DOR) assessed by the investigator based on RECIST 1.1 criteria.(Up to 2 years)
To evaluate Disease Control Rate (DCR) assessed by the investigator based on RECIST 1.1 criteria.(Up to 2 years)
To evaluate Overall Survival (OS) assessed by the investigator based on RECIST 1.1 criteria.(Up to 2 years)
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment.(Up to 2 years)