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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02168725
• Other study ID #: Onconova 08-02
• Secondary ID: COMIRB 14-0565
• Status: Terminated
• Phase: Phase 1
• Start date: June 2014
• Est. completion date: December 2015

Study information

• Verified date: June 2021
• Source: Onconova Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• briciclib

Locations

Country	Name	City	State
United States	University of Colorado Hospital Anschutz Medical Campus	Aurora	Colorado
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Sarah Cannon Research Institute	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Onconova Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarker Concentration or Activity	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).	Up to 1 year
Primary	Number of patients with adverse events	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.	Up to 1 year
Primary	Number of patients with Dose Limiting Toxicity (DLT)	Dose-limiting toxicity is defined as an adverse event that is considered to be drug-related and meets one of the Protocol definitions.	Up to 3 weeks
Primary	Maximum Tolerated Dose	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).	3 weeks
Secondary	Concentration of briciclib in the plasma	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.	24 hours
Secondary	Concentration of briciclib in the urine	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.	24 hours
Secondary	Change in size of tumors	Change in the overall tumor will be determined from the tumor burden at Baseline following Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Up to 1 year