- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03676946
A Clinical Study of PD-L1 Antibody ZKAB001(Drug Code) in Locally Advanced and Metastatic Urothelial Carcinoma
An Open-label, Dose-escalation, Bi-weekly Phase I+II Clinical Trial in Treating Patients With Locally Advanced and Metastatic Urothelial Carcinoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100000
- Recruiting
- Beijing Tumor Hospital
-
Contact:
- Jun Guo, M.D
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- The subject voluntarily gives written informed consent to participate in the study.
- Female and male patients aged between 18 and 75 (inclusive).
- Subjects must have a histologically and/or cytologically confirmed diagnosis of urothelial carcinoma and the recurrence or metastasis is confirmed again after recurrence, and must have failed or are intolerable to standard therapies or for whom no standard therapies exist.
- Must have measurable disease with at least 1 unidimensional measurable lesion (recorded as the maximum diameter) based on RECIST 1.1.
- Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1, with estimated life expectancy of at least 3 months.
- Adequate blood routine, hepatic and renal function:
1)neutrophil count (ANC) absolutely acuity≥1.5 x 109 / L; 2)platelet count≥80 x 109 / L ; 3)hemoglobin≥90 g/L; 4)serum albumin≥28 g/L; 5)bilirubin≤1.5 x ULN (upper limit of normal ); 6)ALT and AST≤1.5 x ULN, such as liver metastasis, ALT (alanine transaminase) and AST≤5 x ULN; 7)serum Cr≤1.25 x ULN or endogenous creatinine clearance≥50 ml/min (according Cockcroft Gault formula).
7.Female patients of reproductive age should take effective contraception during the study period and within 3 months after the study treatment period. The serum or urine human chorionic gonadotropin (HCG) examination must be negative within 7 days before the study was enrolled.
Exclusion Criteria:
- Any active autoimmune disease or history of autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, pituitary inflammation, hyperthyroidism, hypothyroidism, etc.); Patients with vitiligo or asthma in childhood, and still need medical intervention in adult; Patients need bronchodilators for medical intervention of asthma.
- Patients are using immunosuppressive agents, or systemic, or absorbable topical corticosteroid medications to achieve immunosuppressive purposes (doses >10mg/day prednisone or equivalent), which is ongoing 2 weeks before enrollment.
- Have received any form of organ transplantation, including allogeneic stem cell transplantation.
- Known allergy to macromolecular protein inhibitors or any of the components of ZKAB001.
- Suffering from other malignant tumors other than this diseases in 5 years except skin basal cell and squamous cell carcinoma or cervical carcinoma in situ.
- Central nervous system metastases with clinical symptoms (such as cerebral edema and brain metastases requiring corticosteroid intervention). Previous treatment with brain or meningeal metastasis, such as clinical stabilization (MRI) less than 2 months, or systemic corticosteroid (dose >10mg/day prednisone or equivalent) less than 2 weeks.
- Patients with clinical symptoms or heart diseases that cannot be well controlled, such as heart failure above New York Heart Association (NYHA) 2 grade, unstable angina pectoris, myocardial infarction in 1 year, and clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention, left ventricular ejection fraction < 50% at rest as shown in the ultrasound cardiogram.
- Patients who had received radiotherapy, chemotherapy, surgery or molecular targeted therapy before, were given less than 4 weeks or 5 half-life (longer time) after the treatment (if treated with nitrosourea or mitomycin previously, the time interval between the end of chemotherapy and study inclusion was less than 6 weeks); Adverse events caused by previous treatment did not recover to level 1 of CTCAE, except for hair loss.
- Active infection, or unexplained fever> 38.5 degrees during screening period or before the first dose of ZKAB001 (subjects with fever from the tumor could be enrolled upon investigator's decision).
- Human immunodeficiency virus (HIV) positive, syphilis spirochete positive, untreated active hepatitis.
- The patient is participating in other clinical studies or is less than 1 month away from the end of the previous clinical study.
- Patients may need to receive other systemic cancer treatment during study period.
- Prior therapy with an anti-PD 1, anti-PD L1, or anti-CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) antibody (or any other agents that target immunoregulatory receptor).
- Recent history of prophylactic non-cancer vaccination (such as seasonal influenza vaccine and human papillomavirus (HPV) vaccine) within 28 days before screening.
- History of mental drug abuse, alcohol abuse or drug abuse.
- Pregnant or lactating women.
- Any mental condition that prevents the understanding or provision of an informed consent.
- It is determined by the investigator that the patient has other factors that may lead to the termination of the study, such as other serious diseases or serious laboratory test abnormalities or other factors that may affect the safety of the subjects, family or social factors that may affect the study data and sample collection.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: ZKAB001 5mg/kg
Three or six patients will be treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly.
DLT will be observed within 28 days after administration.
|
5mg/kg/times bi-week IV administration of ZKAB001
Other Names:
|
EXPERIMENTAL: ZKAB001 10mg/kg
Three or six patients will be treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly.
DLT will be observed within 28 days after administration.
|
10mg/kg/times bi-week IV administration of ZKAB001
Other Names:
|
EXPERIMENTAL: ZKAB001 15mg/kg
Three or six patients will be treated with the dose of 5 mg/kg/time of ZKAB001 IV bi-weekly.
DLT will be observed within 28 days after administration.
|
15mg/kg/times bi-week IV administration of ZKAB001
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limiting toxicity (DLT)
Time Frame: 28 days after first dose
|
Adverse events of level 3 or above related to the study drug occurring within 28 days after the first dose as assessed by CTCAE v4.0.
|
28 days after first dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximal tolerable dose(MTD)
Time Frame: 28 days after first dose
|
DLT occurs in less than 1/6 subjects, this lower dose is defined as MTD.
|
28 days after first dose
|
The overall response rate(ORR)
Time Frame: through study completion, an average of 2 year
|
The proportion of subjects who achieve the optimal objective response rate (PR or CR).
|
through study completion, an average of 2 year
|
AUC(0-t)
Time Frame: 24 periods or 1 year
|
Area under curve 0-t
|
24 periods or 1 year
|
AUC(INF)
Time Frame: 24 periods or 1 year
|
Area under curve INF
|
24 periods or 1 year
|
Cmax
Time Frame: 24 periods or 1 year
|
Peak concentration
|
24 periods or 1 year
|
Tmax
Time Frame: 24 periods or 1 year
|
Peak time
|
24 periods or 1 year
|
T1/2
Time Frame: 24 periods or 1 year
|
Half life
|
24 periods or 1 year
|
Vss
Time Frame: 24 periods or 1 year
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Steady-state apparent volume of distribution based on plasma concentration
|
24 periods or 1 year
|
Total body clearance(CLT)
Time Frame: 24 periods or 1 year
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Total body clearance
|
24 periods or 1 year
|
Cmin
Time Frame: 24 periods or 1 year
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The trough value at steady state
|
24 periods or 1 year
|
The percentage of the receptors of PD-L1 in CD14+(cluster of differentiation 14+) monocytes and CD3+(cluster of differentiation 3+) T cells
Time Frame: through study completion, an average of 2 year
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To detected the percentage of the receptors of PD-L1 in CD14+ monocytes and CD3+ T cells.
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through study completion, an average of 2 year
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The number of subjects presenting detectable anti drug antibodies (ADAs)
Time Frame: through study completion, an average of 2 year
|
To evaluated the number of subjects presenting detectable anti drug antibodies (ADAs).
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through study completion, an average of 2 year
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Jun Guo, MD, Beijing Tumor Hospital
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NTL-LEES-2017-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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