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

NCT02168725 | Terminated Phase 1

• 2 other identifiers: Onconova 08-02COMIRB 14-0565
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

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.

Conditions

Neoplasms; Advanced Solid Tumor

Keywords

briciclib; Dose escalation; Maximum tolerated dose

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (3)

• 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

Other Outcomes (1)

• Biomarker Concentration or Activity

  Up to 1 year

Study Arms (1)

briciclib

EXPERIMENTAL

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

Interventions

briciclib DRUG

Also known as: ON 013105

briciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed solid tumor (leukemia and lymphoma are excluded)
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Minimum expected life expectancy \> 6 months
• One or more measurable lesion(s) ("target lesion\[s\]") that can be accurately measured in at least 1 dimension
• Willing to adhere to the prohibitions and restrictions specified in the protocol
• The patient must sign an informed consent form (ICF)

You may not qualify if:

• Recent major surgery (within the past 14 days)
• Chemotherapy or dose of other potentially myelosuppressive treatment within 3 weeks prior to Screening (6 weeks for nitrosoureas or mitomycin C)
• No more than a total cumulative dose of 450 mg/m\^2 of prior doxorubicin chemotherapy
• Definitive radiotherapy (\> 10 fractions and maximal area of hematopoietic active Bone Marrow treated greater than 25%) within 4 weeks prior to Screening
• Palliative radiotherapy (≤ 10 fractions) within 2 weeks prior to Screening
• Known brain metastases, except brain metastases that have been previously removed or irradiated and currently have no clinical impact
• 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
• Ascites requiring active medical management, including paracentesis
• Pleural effusion requiring active medical management
• Peripheral bilateral edema requiring active medical management
• Hyponatremia (serum sodium value less than 130 mEq/L)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to briciclib
• 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
• History of myocardial infarction
• 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

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (3)

University of Colorado Hospital Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

ON 013105

Study Officials

• Antonio Jimeno, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2014
• First Posted: June 20, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: June 22, 2021

Record last verified: 2021-06

Locations

US (3)