A Phase II Study to Evaluate the Efficacy and Safety of TLC388 in Advanced/Metastatic RCC Patients

Study Overview
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Brief Summary
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INVESTIGATIONAL PRODUCT: TLC388 (Lipotecan*) *Lipotecan is a drug product of TLC388 HCl. PHASE OF DEVELOPMENT: Phase II No. OF PATIENTS: Approximately 40 (Stage I: 15 evaluable patients, Stage II: 25 evaluable patients) STUDY OBJECTIVES: Primary • To evaluate non-progression disease (non-PD) rate at the end of cycle 6 Secondary To evaluate progression free survival (PFS) To evaluate overall survival (OS) To evaluate the duration of non-PD To evaluate objective response rate (ORR; where ORR= CR+PR) and duration To evaluate the safety profile of TLC388 To evaluate change in health-related quality of life (HRQOL) at the end of cycle 6 STUDY DESIGN: This is a Phase II, open-label, single-arm, multi-centre study to evaluate TLC388 monotherapy in patients with locally advanced and/or metastatic renal cell carcinoma (RCC).

Detailed Description
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A Phase II, open-label, single-arm, multi-center study to evaluate TLC388 monotherapy in patients with locally advanced and/or metastatic RCC. The study consisted of a Screening/Baseline Period, a Treatment Period and a post-treatment Follow-Up Period for PFS and OS. Patients were to be recruited at two stages. Stage I recruited 15 evaluable patients, who had completed at least 2 cycles of treatment with one tumor assessment. If ≤ 5 patients did not develop PD at the end of cycle 6 per RECIST, no patients were to be recruited for Stage II and the study was to be closed. If > 5 patients did not develop PD at the end of cycle 6, a total of 40 evaluable patients (additional 25 evaluable patients for Stage II) were to be recruited thereafter.

Official Title
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An Open-Label, Single-Arm, Multi-center Phase II Study to Evaluate the Efficacy and Safety of TLC388 in Patients With Advanced/Metastatic Renal Cell Carcinoma

Conditions
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Advanced/Metastasis Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Lipotecan


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Adult patients defined by age ≥ 18 years Histologically confirmed Renal cell carcinoma (RCC) Locally advanced or metastatic RCC. Locally advanced RCC: defined as a stage T3/T4 disease, not amenable to curative surgery or radiation therapy, with involvement of renal vein/vena cava/peripelvic and perirenal fat/adrenal gland, or invasion beyond Gerota's fascia. Metastatic RCC: equivalent to Stage IV RCC, according to American Joint Committee on Cancer (AJCC) staging Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤ 2. But for the patient with failure of ≥ 2 prior target therapies, ECOG should be ≤ 1. Documented RCC disease with measurable or non-measurable lesion on imaging by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria Documented treatment failure of at least 1 prior target therapy (sorafenib, sunitinib pazopanib or other VEGF TKI, bevacizumab, temsirolimus, everolimus or other mTOR inhibitor) for advanced or metastatic RCC. If treatment-naïve, patients with poor prognosis features according to Memorial Sloan-Kettering Cancer Centre (MSKCC) risk criteria are acceptable Any acute or chronic adverse effects of prior therapy have resolved to <Grade 2 as determined by CTCAE v4.0 criteria Laboratory values at screening: Absolute neutrophil count ≥ 1,500 /mm3; Platelets ≥ 100,000 /mm3; Hemoglobin ≥ 9.0 g/dL; Total bilirubin ≤ 1.5 times the upper limit of normal; AST (SGOT) ≤ 2.5 times the upper limit of normal; ALT (SGPT) ≤ 2.5 times the upper limit of normal; Serum creatinine ≤ 2 times the upper limit of normal; EXCLUSION CRITERIA: Pregnancy or lactation. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrolment. Male and female patients of childbearing potential must agree to use appropriate birth control (barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices) during the entire duration of the study, or the patient must be surgically sterile (with documentation in the patient's medical records) Receipt of any chemotherapy for RCC Had cardiac angioplasty or stenting event, myocardial infarction or unstable angina within 3 months of study entry Persistent QTc >450 ms for males, or >470 ms for females, according to Fridericia's correction Patients with Grade 3 or greater hyponatremia at screening History of Class III or IV congestive heart failure according to New York Heart Association (NYHA) classification History of another malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, and not disease free ≥5 years History or presence of central nervous system (CNS) metastasis or leptomeningeal tumors as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam History of human immunodeficiency virus infection Presence of active, uncontrolled infection Radiotherapy received within 4 weeks prior to baseline Use of any investigational agents within 4 weeks of baseline Major surgery within 4 weeks prior to baseline Receipt of radiotherapy to >25 % of bone marrow Concomitant treatment with, or anticipated use of, pharmaceutical or herbal agents which are potent inhibitors or inducers of cytochrome P450 enzymes (Appendix D1), unless approved by the Sponsor Uncontrolled intercurrent illness that would jeopardize patient safety, or interfere with the objectives of the protocol, or limit patient compliance with study requirements, as determined by the Investigator

Ages Eligible for Study
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Minimum Age: 18 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: Lipotecan, injection for chemotherapy<br>Patients receive TLC388 (50 mg/m2) given as a 30-minute IV infusion, on Days 1, 8, and 15 of a 28-day cycle. | Drug: Lipotecan<br> <br> * Other names: TLC388;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-progression disease (non-PD) rate at the end of cycle 6 | Non-progression disease rate after cycle 6 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | Progression free survival | 3 years | 
| Overall survival (OS) | Overall sruvival | 3 years | 
| Duration of non-PD | Non-progression disease rate (overall) | 3 years | 
| Objective response rate (ORR; where ORR= CR+PR) and duration | Objective response rate and duration | 3 years | 
| Safety profile of TLC388 | Serious/ Adverse Events | 3 years | 
| Change in health-related quality of life (HRQOL) at the end of cycle 6 | Quality of life after cycle 6 | 6 months |