A Single Arm, Open-label,Phase Ib Study of CT053PTSA in Preciously Treated Patients With Advanced and Metastatic RCC

Study Overview
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Brief Summary
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This is a phase Ib,single arm,open label study evaluating the safety and efficacy of CT053PTSA in patients with advanced and metastatic renal cell cancer who have progressed from previous treatment

Detailed Description
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This study is being carried out in two parts,part 1 and part 2. Part 1: This is the dose-escalation part. The primary purpose of the part 1 portion is to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and recommend the appropriate doses of CT053PTSA for further study Part 2: This is the expansion part.The part 2 portion of this study will continue to evaluate the safety and efficacy of CT053PTSA at the appropriate dose recommended in Part 1,in patients with advanced and metastatic RCC

Official Title
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A Single Arm, Open-label,Phase Ib Study of CT053PTSA in Preciously Treated Patients With Advanced and Metastatic Renal Cell Cancer

Conditions
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Renal Cell Cancer Metastatic

Intervention / Treatment
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* Drug: CT053PTSA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed renal cell cancer.Patients must be diagnosed with advanced or metastatic disease,disease progressed to previous treatment . Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) Toxicity recovered to NCI CTCAE v.4.03 Grade ≤1 from previous treatments (except alopecia) ECOG performance status (PS) 0 or 1 Life expectancy of ≥ 12 weeks Adequate organ function Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol Exclusion Criteria: Chemotherapy,radiotherapy,immunotherapy and targeted therapy less than 4 months prior to administration. Symptomatic, untreated or unstable central nervous system metastases Uncontrolled hypertension that require anti-hypertensive agents to control, or systolic blood pressure (BP) >140mmHg or diastolic BP >90 mmHg before the first administration (BP is the mean blood pressure of two measures that 1 hours interval or above) Doppler ultrasound evaluation：Left ventricular ejection fraction < 50% Significantly clinical arrhythmia or symptomatic bradycardia, or male with QTCF > 450 ms or female with QTCF > 470 ms, or patients with a history of torsion or congenital QT prolonged syndrome long QT syndrome Certain factors that would preclude adequate absorption of CT053PTSA and gefitinib (eg. unable to swallow, chronic diarrhea, intestinal obstruction) Patients with evidence of bleeding tendency, including the following cases: gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above; or melena or hematemesis within 2 months; or visceral bleeding that may occur considered by investigator History of organ transplantation Any disease of the following bellowed within 12 months prior to administration: Myocardial infarction, severe angina, or unstable angina, coronary or peripheral artery bypass graft, congestive heart failure Pulmonary embolism or cerebrovascular events (including transient ischemic attack)within 6 months prior to administration Infection of HIV Patients with infection of HBV or HCV. Patients with positive of HBsAg or HBcAb,and HBV-DNA can be measured (>500IU/ml). Patients with positive of anti-HCV,and HCV-RNA can be measured by PCR. Other malignancies within 5 years prior to enrollment, with the exception of carcinoma in situ of the cervix, basal or squamous cell skin cancer Pregnant or lactating woman Any other reason the investigator considers the patient is not suitable to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT053PTSA<br>60-100mg | Drug: CT053PTSA<br>* Patients will received oral CT053PTSA once daily until disease progression or intolerable toxicity or subject's withdrawal from treatment ,each cycle is defined as 28 days<br>* Other names: Ningetinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1(dose-escalation part):Maximum Tolerated Dose (MTD) | The maximum tolerated dose (MTD) of the CT053PTSA will be determined according to incidence of dose-limiting toxicity (DLT) assessed by NCI CTCAEv4.03 | Cycle 1 Day 1 to Cycle 1 Day 28 | 
| Part 2 (expansion part):Overall Response Rate | Overall response rate (ORR),defined as a partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Evaluation Criteria in Solid Tumors as assessed by RECIST1.1 | up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events (AEs) as a measure of safety and tolerability | Safety and tolerability will be assessed through AEs, via monitoring changes in physical examination, clinical laboratory parameters, vital signs and ECGs | up to approximately 24 months | 
| Disease Control Rate (DCR) | DCR, proportion of patients with best overall response of CR, PR or SD | up to approximately 24 months | 
| Progression-free Survival (PFS) | PFS, defined as time from date of treatment to disease progression or death due to any cause | up to approximately 24 months | 
| Duration of Response (DOR) | DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause | up to approximately 24 months | 
| Overall Survival (OS) | OS, defined as time from date of treatment to death due to any cause | up to approximately 24 months | 
| Maximum observed plasma concentration (Cmax) | to assess the pharmacokinetic profile | Cycle 1 Day1 and Day 28 | 
| Time of maximum observed plasma concentration (Tmax) | to assess the pharmacokinetic profile | Cycle 1 Day1 and Day 28 | 
| Area under the plasma concentration time curve (AUC) | to assess the pharmacokinetic profile | Cycle 1 Day1 and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RCC