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

A Phase I, Dose-escalation Study of the Safety, Pharmacokinetics and Efficacy of Weekly Intravenous Briciclib in Patients With Advanced Solid Tumors


Lead Sponsor: Onconova Therapeutics, Inc.

Source Onconova Therapeutics, Inc.
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.

Overall Status Suspended
Start Date June 2014
Completion Date November 2019
Primary Completion Date August 2019
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of patients with adverse events Up to 1 year
Number of patients with Dose Limiting Toxicity (DLT) Up to 3 weeks
Maximum Tolerated Dose 3 weeks
Secondary Outcome
Measure Time Frame
Concentration of briciclib in the plasma 24 hours
Concentration of briciclib in the urine 24 hours
Change in size of tumors Up to 1 year
Enrollment 54

Intervention Type: Drug

Intervention Name: briciclib

Arm Group Label: briciclib

Other Name: ON 013105



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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Antonio Jimeno, MD, PhD Principal Investigator University of Colorado, Denver
University of Colorado Hospital Anschutz Medical Campus | Aurora, Colorado, 80045, United States
Roswell Park Cancer Institute | Buffalo, New York, 14263, United States
Sarah Cannon Research Institute | Nashville, Tennessee, 37203, United States
Location Countries

United States

Verification Date

July 2018

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: briciclib

Type: Experimental

Description: The starting dose of briciclib in the Escalation Stage will be 17 mg/week, with subsequent dose escalation levels of 35 mg, 70 mg, 140 mg, 280 mg, 560 mg, and 1120 mg. The dose of briciclib in the RPTD Confirmation Stage will be the dose as determined during the escalation stage. At each dose level, briciclib will be administered as a 2-hour intravenous infusion, once-a-week per 3-week cycles.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)