A Study on Toripalimab Plus Nab-Paclitaxel With or Without Cisplatin as First-line Treatment of Urothelial Carcinoma

NCT04211012 | Unknown Phase 2

• 1 other identifier: BJCH-UC-1015
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) by RECIST 1.1

  ORR based on RECIST 1.1

  Up to 2 years

Secondary Outcomes (7)

• To evaluate Progression-free Survival (PFS) assessed by the investigator based on RECIST 1.1 criteria.

  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 Time to Response (TTR) 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

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Drug: Toripalimab plus Nab-Paclitaxel +/- cisplatin

Interventions

Toripalimab plus Nab-Paclitaxel +/- cisplatin DRUG

Toripalimab injection (JS001): 240mg, i.v.gtt, q3w; Nab-Paclitaxel: 260mg/m2, i.v.gtt, q3w Cisplatin: total dosage of 70 mg/m2 i.v.gtt, q3w，, complete all doses within the first 2 days of each cycle. Study treatment will be continued until disease progression or intolerable toxicity, or withdrawal at the discretion of the investigator or the subject, loss to follow-up, or initiation of other anti-cancer therapy, or death, whichever occurs first. Toripalimab will be administered no more than 2 years,and nab-paclitaxel with or without cisplatin will be administered up to 6 cycles.. If the subject is intolerable to cisplatin treatment according to the investigator's judgment, JS001 + Nab-Paclitaxel may be dosed. Dosing sequence: Toripalimab, Nab-Paclitaxel, cisplatin

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Coagulation function: international normalized ratio (INR) or prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless the subject is receiving anticoagulation therapy, PT or aPTT just needs to be within the expected therapeutic range of the anticoagulant).
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• Men of reproduction ability or women of pregnant possibility \[amputation of uterus, bilateral oophorectomy or bilateral tubal ligation not performed, or prior to menopause (total menopause ≥1 year)\] must adopt highly-effective contraceptive methods (e.g. oral contraceptives, intrauterine contraceptive device, abstinence of sexual intercourse or barrier contraception in combination with spermatocide) during the whole study, and continue contraception for 12 months after the last dose of study drug.

You may not qualify if:

• 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;
• Uncontrolled concomitant diseases including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina, arrhythmia, interstitial lung disease, or mental illness/social conditions consistent with the following characteristics: restricting study-specified compliance, significantly increasing the risk of developing AEs, or affecting patients' ability to provide informed consent form.
• Known human immunodeficiency virus (HIV) infection (positive HIV antibody);
• Active HBV or HCV infection; HBV DNA must be detected for patients with positive HbsAg or HBcAb at the screening; if HBV DNA test is positive at the same time (limit of quantitation 500 IU/ml, or reaching the positive value detected at the study center); Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Active tuberculosis;
• Allergies and adverse drug allergy reaction; Known hypersensitivity reactions to Toripalimab or any ingredient of Toripalimab Injection; History of serious hypersensitivity to nab-paclitaxel, cisplatin, or its preventive medication;
• Subjects with active central nervous system (CNS) metastasis will be excluded. Patients who have prior therapies for brain or meningeal metastasis and has been stabilized for ≥ 3 months and has discontinued systemic steroids therapy (\>10 mg/day prednisone or equivalent) \> 4 weeks prior to enrollment could be included. If the CNS metastasis can be adequately treated and meet the requirement specified in the enrollment criteria, and the neurological symptoms can be recovered to ≤CTCAE grade 1 prior to enrollment (except the residual sign or symptom related with CNS treatment) for at least two weeks, the subject can participate in the study;

Sponsors & Collaborators

• Jun Guo: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, No.52 Fucheng Road, Haidian District, Beijing, China, 100142, China

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: November 22, 2019
• First Posted: December 26, 2019
• Study Start: November 30, 2020
• Primary Completion: January 30, 2022
• Study Completion: January 30, 2023
• Last Updated: November 13, 2020

Record last verified: 2020-11

Locations

CN (1)