NeoplasmsPhase 1NCT02168725
Dose-escalation, Safety and Pharmacokinetic Study of Briciclib in Advanced Solid Tumors
A Phase 1 study testing briciclib in people with Neoplasms and Advanced Solid Tumor, run by Traws Pharma, Inc. at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Advanced Solid Tumor
- What is being tested?
- briciclib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2014to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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
- Patients who are positive for human immunodeficiency virus type 1 (HIV-1) and are receiving combination anti-retroviral therapy
- Hemoglobin (Hgb) < 9 g/dL
- White Blood Cell count (WBC) < 4,000/µL
- Absolute Neutrophil Count (ANC) < 1,500/µL
- Platelet (PLT) count ≤ 100,000/µL
- Total bilirubin greater than 1.5 x the institutional upper limit of normal (ULN)
- 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
- Serum creatinine > 2 x ULN
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Colorado Hospital Anschutz Medical Campus
Aurora, Colorado, 80045
Roswell Park Cancer Institute
Buffalo, New York, 14263
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
About this study
Official title: A Phase I, Dose-escalation Study of the Safety, Pharmacokinetics and Efficacy of Weekly Intravenous Briciclib in Patients With Advanced Solid Tumors
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.
Read the 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
- Being tested
- briciclib
- Keywords
- briciclib, Dose escalation, Maximum tolerated dose
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
briciclibDrug
Also called ON 013105
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: briciclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Measured: 3 weeks
Secondary outcomes (3)
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.
Measured: 24 hours
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.
Measured: 24 hours
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.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2014 (estimated)
- Study startJun 2014
- Primary completionDec 2015
- Study completionDec 2015
Why it stopped: The study was placed on hold by the FDA due to manufacturing issues and was not restarted.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Traws Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Antonio Jimeno, MD, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02168725
- Sponsor's protocol ID
- Onconova 08-02
- Other IDs
- COMIRB 14-0565
- Status last verified
- Jun 2021
- First submitted
- 18 Jun 2014
- Last updated
- 22 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Dose-escalation Study of the Safety, Pharmacokinetics and Efficacy of Weekly Intravenous Briciclib in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02168725
- Acronym / sponsor ID
- Onconova 08-02
- Conditions
- Neoplasms, Advanced Solid Tumor
- Keywords
- briciclib, Dose escalation, Maximum tolerated dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was placed on hold by the FDA due to manufacturing issues and was not restarted.
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 20 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| briciclib | Experimental | Drug: briciclibThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| briciclibAlso: ON 013105 | Drug | briciclib |
Primary outcome
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.
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.
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).
3 secondary outcomes
Concentration of briciclib in the plasma
Time frame: 24 hours
Concentration of briciclib in the urine
Time frame: 24 hours
Change in size of tumors
Time frame: Up to 1 year
Results and safety
The study was stopped early (reason given: The study was placed on hold by the FDA due to manufacturing issues and was not restarted.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Jimeno, MD, PhD principal investigator
University of Colorado, Denver
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing briciclib in people with Neoplasms and Advanced Solid Tumor, run by Traws Pharma, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was placed on hold by the FDA due to manufacturing issues and was not restarted.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with adverse events (time frame: Up to 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2021.