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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02168725
Recruitment Status : Suspended
First Posted : June 20, 2014
Last Update Posted : August 1, 2018
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Neoplasms Advanced Solid Tumor Drug: briciclib Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : June 2014
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : November 2019

Arm Intervention/treatment
Experimental: 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.
Drug: briciclib
Other Name: ON 013105

Primary Outcome Measures :
  1. Number of patients with adverse events [ Time Frame: 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.

  2. Number of patients with Dose Limiting Toxicity (DLT) [ Time Frame: 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.

  3. Maximum Tolerated Dose [ Time Frame: 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).

Secondary Outcome Measures :
  1. Concentration of briciclib in the plasma [ Time Frame: 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.

  2. Concentration of briciclib in the urine [ Time Frame: 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.

  3. Change in size of tumors [ Time Frame: 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.

Other Outcome Measures:
  1. Biomarker Concentration or Activity [ Time Frame: 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).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02168725

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United States, Colorado
University of Colorado Hospital Anschutz Medical Campus
Aurora, Colorado, United States, 80045
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Onconova Therapeutics, Inc.
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Principal Investigator: Antonio Jimeno, MD, PhD University of Colorado, Denver
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Responsible Party: Onconova Therapeutics, Inc. Identifier: NCT02168725    
Other Study ID Numbers: Onconova 08-02
COMIRB 14-0565 ( Other Identifier: Univ. of Colorado Denver Multiple Institutional Review Board )
First Posted: June 20, 2014    Key Record Dates
Last Update Posted: August 1, 2018
Last Verified: July 2018
Keywords provided by Onconova Therapeutics, Inc.:
Dose escalation
Maximum tolerated dose
Additional relevant MeSH terms:
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