Dose-escalation, Safety and Pharmacokinetic Study of Briciclib in Advanced Solid Tumors

Inclusion Criteria

• Histologically confirmed solid tumor (leukemia and lymphoma are excluded)
• Malignancy that is incurable and for which standard (FDA approved or established standard clinical practice) curative, or palliative measures do not exist or are no longer effective
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Minimum expected life expectancy > 6 months
• One or more measurable lesion(s) ("target lesion[s]") that can be accurately measured in at least 1 dimension
• Willing to adhere to the prohibitions and restrictions specified in the protocol
• The patient must sign an informed consent form (ICF)

Exclusion Criteria

• Recent major surgery (within the past 14 days)
• Chemotherapy or dose of other potentially myelosuppressive treatment within 3 weeks prior to Screening (6 weeks for nitrosoureas or mitomycin C)
• No more than a total cumulative dose of 450 mg/m^2 of prior doxorubicin chemotherapy
• Definitive radiotherapy (> 10 fractions and maximal area of hematopoietic active Bone Marrow treated greater than 25%) within 4 weeks prior to Screening
• Palliative radiotherapy (≤ 10 fractions) within 2 weeks prior to Screening
• Known brain metastases, except brain metastases that have been previously removed or irradiated and currently have no clinical impact
• Residual adverse events due to previously administered agents (except alopecia, stable residual neuropathy, and residual hand, foot syndrome) that have not recovered to Grade 1 or below in severity level (based on NCI CTCAE) before Screening
• Ascites requiring active medical management, including paracentesis
• Pleural effusion requiring active medical management
• Peripheral bilateral edema requiring active medical management
• Hyponatremia (serum sodium value less than 130 mEq/L)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to briciclib
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, bleeding, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of myocardial infarction
• Any other concurrent investigational agent or chemotherapy, radiotherapy, hormonotherapy, or immunotherapy. Exceptions are long-term hormonals for prostate (eg, goserelin) and octreotide for neuroendocrine malignancies
• Patients who are positive for human immunodeficiency virus type 1 (HIV-1) and are receiving combination anti-retroviral therapy
• Hemoglobin (Hgb) < 9 g/dL
• White Blood Cell count (WBC) < 4,000/µL
• Absolute Neutrophil Count (ANC) < 1,500/µL
• Platelet (PLT) count ≤ 100,000/µL
• Total bilirubin greater than 1.5 x the institutional upper limit of normal (ULN)
• Aspartate transaminase (AST) or alanine transaminase (ALT) ≥ 2.5 x institutional ULN. If liver function abnormalities are due to metastatic disease, patients are eligible provided the ALT and AST are < 5 x ULN
• Serum creatinine > 2 x ULN