Advanced Solid Tumor, Neoplasms
Conditions
Keywords
briciclib, Dose escalation, Maximum tolerated dose
Brief summary
The main objectives of this study are to determine the safety profile of briciclib, an experimental anti-cancer drug, as it is administered intravenously once weekly as escalating doses in adult patients with advanced cancer and solid tumors, and to determine the highest dose of briciclib that can be safely given. Secondary objectives are to determine how the amount of briciclib in circulation changes over time and how much briciclib gets into the urine for excretion, and to document potential anti-tumor effects of briciclib.
Detailed description
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.
Interventions
DRUGbriciclib
Sponsors
Traws Pharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | 3 weeks | Maximum Tolerated Dose (MTD) will be defined during the Dose Escalation Stage based on evaluation of the number of patients with Dose-limiting Toxicity (DLT). The MTD will be used to determine the Recommended Phase 2 Dose (RPTD). |
| Number of patients with adverse events | Up to 1 year | Adverse events will be grouped by system organ class (SOC) and preferred term (PT) using the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA), and will be summarized by worst grade according to NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. |
| Number of patients with Dose Limiting Toxicity (DLT) | Up to 3 weeks | Dose-limiting toxicity is defined as an adverse event that is considered to be drug-related and meets one of the Protocol definitions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in size of tumors | Up to 1 year | Change in the overall tumor will be determined from the tumor burden at Baseline following Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
| Concentration of briciclib in the plasma | 24 hours | The amount of briciclib in the plasma of patients in the Recommended Phase 2 Dose (RPTD) Confirmation stage only will be measured by a validated Liquid Chromatography-Mass Spectroscopy (LC-MS) method. Pharmacokinetic parameters will be derived from the concentration versus time values. |
| Concentration of briciclib in the urine | 24 hours | The amount of briciclib in the urine of patients in the Recommended Phase 2 Dose (RPTD) Confirmation stage only will be measured by a validated Liquid Chromatography-Mass Spectroscopy (LC-MS) method. Pharmacokinetic parameters will be derived from the concentration versus time values. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Biomarker Concentration or Activity | Up to 1 year | An exploratory objective of this study is to evaluate the biological effect of briciclib on cell-cycle pathways, cyclin D1, and other potential surrogate biomarker(s) of efficacy and/or toxicity in tumor tissue and peripheral blood mononuclear cells (PBMNC). |
Countries
United States
Outcome results
None listed