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
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 (Moch et al., 2009). 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. An ECOG of ≤ 1
for the patient with failure of >= 2 prior target therapies is acceptable
- 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
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