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

Launched by TRAWS PHARMA, INC. · Jun 19, 2014

Keywords

ClinConnect Summary

This will be a Phase I, 2-stage, open-label, dose-escalating, multicenter study of the 2-hour, once-a-week intravenous (IV) administration of briciclib in 3-week cycles, in up to 54 adult patients with advanced cancer and solid tumors. The study will be conducted in 2 stages: a dose-escalation stage to determine the Maximum Tolerated Dose (MTD) and a Recommended Phase 2 Dose (RPTD) confirmation stage. Patients with stable disease (SD) or response may remain treated on study until progression.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Histologically confirmed solid tumor (leukemia and lymphoma are excluded)
• • 2. 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
• • 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• • 4. Minimum expected life expectancy \> 6 months
• • 5. One or more measurable lesion(s) ("target lesion\[s\]") that can be accurately measured in at least 1 dimension
• • 6. Willing to adhere to the prohibitions and restrictions specified in the protocol
• • 7. The patient must sign an informed consent form (ICF)
• Exclusion Criteria:
• • 1. Recent major surgery (within the past 14 days)
• • 2. Chemotherapy or dose of other potentially myelosuppressive treatment within 3 weeks prior to Screening (6 weeks for nitrosoureas or mitomycin C)
• • 3. No more than a total cumulative dose of 450 mg/m\^2 of prior doxorubicin chemotherapy
• • 4. Definitive radiotherapy (\> 10 fractions and maximal area of hematopoietic active Bone Marrow treated greater than 25%) within 4 weeks prior to Screening
• • 5. Palliative radiotherapy (≤ 10 fractions) within 2 weeks prior to Screening
• • 6. Known brain metastases, except brain metastases that have been previously removed or irradiated and currently have no clinical impact
• • 7. 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
• • 8. Ascites requiring active medical management, including paracentesis
• • 9. Pleural effusion requiring active medical management
• • 10. Peripheral bilateral edema requiring active medical management
• • 11. Hyponatremia (serum sodium value less than 130 mEq/L)
• • 12. History of allergic reactions attributed to compounds of similar chemical or biologic composition to briciclib
• • 13. 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
• • 14. History of myocardial infarction
• • 15. 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
• • 16. Patients who are positive for human immunodeficiency virus type 1 (HIV-1) and are receiving combination anti-retroviral therapy
• • 17. Hemoglobin (Hgb) \< 9 g/dL
• • 18. White Blood Cell count (WBC) \< 4,000/µL
• • 19. Absolute Neutrophil Count (ANC) \< 1,500/µL
• • 20. Platelet (PLT) count ≤ 100,000/µL
• • 21. Total bilirubin greater than 1.5 x the institutional upper limit of normal (ULN)
• • 22. 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
• • 23. Serum creatinine \> 2 x ULN