Clinical trial NCT02168725: Dose-escalation, Safety and Pharmacokinetic Study of Briciclib in Advanced Solid Tumors
Official title: A Phase I, Dose-escalation Study of the Safety, Pharmacokinetics and Efficacy of Weekly Intravenous Briciclib in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Advanced Solid Tumor
Keywords: briciclib
Dose escalation
Maximum tolerated dose
Lead sponsor: Traws Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2014-06-20
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: Up to 1 year
measure: Number of patients with Dose Limiting Toxicity (DLT)
timeFrame: Up to 3 weeks
measure: Maximum Tolerated Dose
timeFrame: 3 weeks
Secondary outcomes:
measure: Concentration of briciclib in the plasma
timeFrame: 24 hours
measure: Concentration of briciclib in the urine
timeFrame: 24 hours
measure: Change in size of tumors
timeFrame: Up to 1 year
Other outcomes:
measure: Biomarker Concentration or Activity
timeFrame: Up to 1 year
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Medical Campus
state: Colorado
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: University of Colorado, Denver
name: Antonio Jimeno, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: