Trial record 1 of 1 for:    NCT02168725
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Dose-escalation, Safety and Pharmacokinetic Study of Briciclib in Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Onconova Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Onconova Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02168725
First received: June 18, 2014
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Neoplasms
Advanced Solid Tumor
Drug: briciclib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Onconova Therapeutics, Inc.:

Primary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    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.

  • Number of patients with Dose Limiting Toxicity (DLT) [ Time Frame: Up to 3 weeks ] [ Designated as safety issue: Yes ]
    Dose-limiting toxicity is defined as an adverse event that is considered to be drug-related and meets one of the Protocol definitions.

  • Maximum Tolerated Dose [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Concentration of briciclib in the plasma [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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.

  • Concentration of briciclib in the urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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.

  • Change in size of tumors [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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:
  • Biomarker Concentration or Activity [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 54
Study Start Date: June 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02168725

Contacts
Contact: Michael Kurman, MD 201-410-3205 mkurman@onconova.us

Locations
United States, Colorado
University of Colorado Hospital Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Antonio Jimeno, MD, PhD         
Sponsors and Collaborators
Onconova Therapeutics, Inc.
Investigators
Principal Investigator: Antonio Jimeno, MD, PhD University of Colorado, Denver
  More Information

No publications provided

Responsible Party: Onconova Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02168725     History of Changes
Other Study ID Numbers: Onconova 08-02, COMIRB 14-0565
Study First Received: June 18, 2014
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Onconova Therapeutics, Inc.:
briciclib
Dose escalation
Maximum tolerated dose

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on September 18, 2014