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

NCT ID: NCT02168725

Last Updated: 2021-06-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2015-12-31

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.

Conditions

Neoplasms; Advanced Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

briciclib

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.

Group Type: EXPERIMENTAL

briciclib

Intervention Type: DRUG

Interventions

briciclib

Intervention Type: DRUG

Other Intervention Names

ON 013105

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Traws Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Jimeno, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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, United States

Countries

United States

Other Identifiers

COMIRB 14-0565

Identifier Type: OTHER

Identifier Source: secondary_id

Onconova 08-02

Identifier Type: -

Identifier Source: org_study_id