Hedgehog PathwayPhase 1NCT00670189
A Phase 1 Study of BMS-833923 (XL139) in Subjects With Advanced or Metastatic Cancer
A Phase 1 study testing BMS-833923 (XL139) in people with Hedgehog Pathway and Smoothened, run by Bristol-Myers Squibb at 3 sites in 2 countries.
Trial summary
The purpose of this study is to determine the safety of BMS-833923 (XL139) in patients with advanced or metastatic cancers and determine the recommended phase 2 dose range and schedule Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hedgehog Pathway, Smoothened, Basal Cell Carcinoma (BCC)
- What is being tested?
- BMS-833923 (XL139)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Jul 2008to May 2014
- 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
- Advanced or metastatic cancer (excluding cancer in the blood) or uncontrolled basal cell nevoid syndrome or sporadic basal cell carcinoma
- Primary or metastatic tumor site accessible for biopsy
- Ability to swallow capsules
- Subjects with histologically confirmed, advanced stage IIIB or stage IV non-small cell lung cancer (NSCLC) with a primary histology of squamous carcinoma who have received prior systemic therapy for advanced NSCLC will be enrolled in Part 3
Who cannot join
- Uncontrolled brain metastasis
- Significant cardiovascular disease
- Inadequate blood counts
- Inadequate liver, kidney or lung function
- Gastrointestinal disease within last 3 months
- Infection with Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C or exposure to attenuated active immunizations
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Southwest Texas Addiction Research And Tech (Start) Center
San Antonio, Texas, 78229
About this study
Official title: A Phase 1 Multiple Ascending Dose Study of BMS-833923 in Subjects With Advanced or Metastatic Solid Tumors
The purpose of this study is to determine the safety of BMS-833923 (XL139) in patients with advanced or metastatic cancers and determine the recommended phase 2 dose range and schedule
- Conditions
- Hedgehog Pathway, Smoothened, Basal Cell Carcinoma (BCC), Basal Cell Nevoid Syndrome (BCNS)
- Being tested
- BMS-833923 (XL139)
- Medical subject headings
- Carcinoma, Basal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-833923 (XL139)Drug
Capsules, Oral, 30 mg starting; dose escalation, Once daily, 37 days; additional days if receiving benefit
| Study group | Role | What they receive |
|---|---|---|
| BMS-833923 | Experimental | Not described Receives: Drug: BMS-833923 (XL139) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Use National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) to establish the maximum tolerated dose, a recommended Phase 2 dose range and schedule, and safety profile of BMS-833923
Use NCI CTCAE to monitor safety assessments including physical findings, laboratory tests, and radiographic assessments to establish the maximum tolerated dose and recommended Phase 2 dose range and schedule of BMS-833923
Measured: On average a minimum of 60 days up to 3 years
Secondary outcomes (12)
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Maximum observed plasma concentration (Cmax)
Measured: Study day 1-7, 36
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Time of maximum observed plasma concentration (Tmax)
Measured: Study day 1-7, 36
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)] of BMS-833923 (XL139)
Measured: Study day 1-7
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-833923 (XL139)
Measured: Study day 1-7
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Plasma half-life (T-HALF) of BMS-833923 (XL139)
Measured: Study day 1-7
Pharmacokinetic parameters of BMS-833923 (XL139) during daily dosing: Minimum observed plasma concentration (Cmin) of BMS-833923 (XL139)
Measured: Study day 1, 8, 15, 22, 29, 36, 64, and 92
Pharmacokinetic parameters of BMS-833923 (XL139) during daily dosing: Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-833923 (XL139)
Measured: Study day 36
To assess the pharmacodynamic effects of BMS-833923 (XL139) on Hedgehog (HH) pathway activation in skin by evaluation of biomarkers such as, but not limited to GLI-1 protein or mRNA expression using immunohistochemistry (IHC) or RT-PCR in a skin biopsies
glioma-associated oncogene family of transcription factors (GLI)
Measured: At screening (baseline) and between days 22 and 36 of treatment
To assess the pharmacodynamic effects of BMS-833923 (XL139) on HH pathway activation in subjects' tumors by evaluation of protein and mRNA of biomarkers such as, but not limited to GLI-1, in pre- and during-treatment tumor samples
glioma-associated oncogene family of transcription factors (GLI)
Measured: At screening (baseline) and between days 22 and 36 of treatment. At screening only for NSCLC patients
To describe any preliminary evidence of anti-tumor activity of BMS-833923 (XL139)
Tumor assessments by computed tomography (CT)
Measured: Every 8 weeks until disease progression
Safety profile of multiple doses of BMS-833923
Medical review of adverse event reports
Measured: Adverse event reports: On average a minimum of 60 days up to 3 years
Safety profile of multiple doses of BMS-833923
The results of vital sign measurements, electrocardiogram (ECGs), pulmonary function tests, multigated radionuclide angiography (MUGA) or echocardiograms, physical examinations, and clinical laboratory tests
Measured: Conducted at least on days 1, 8, 15, 22 and 36 of the first 36-day cycle and then monthly or biweekly for the first 6 months, then monthly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2008 (estimated)
- Study startJul 2008
- Primary completionApr 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hedgehog PathwayStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Exelixis
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00670189
- Sponsor's protocol ID
- CA194-002
- Status last verified
- Aug 2014
- First submitted
- 29 Apr 2008
- Last updated
- 15 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Multiple Ascending Dose Study of BMS-833923 in Subjects With Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT00670189
- Acronym / sponsor ID
- CA194-002
- Conditions
- Hedgehog Pathway, Smoothened, Basal Cell Carcinoma (BCC), Basal Cell Nevoid Syndrome (BCNS)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Collaborators
- Exelixis
- Study start
- Jul 2008
- Primary completion
- Apr 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 1 May 2008 (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 purpose of this study is to determine the safety of BMS-833923 (XL139) in patients with advanced or metastatic cancers and determine the recommended phase 2 dose range and schedule
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BMS-833923 | Experimental | Drug: BMS-833923 (XL139) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Advanced or metastatic cancer (excluding cancer in the blood) or uncontrolled basal cell nevoid syndrome or sporadic basal cell carcinoma
- Primary or metastatic tumor site accessible for biopsy
- Ability to swallow capsules
- Subjects with histologically confirmed, advanced stage IIIB or stage IV non-small cell lung cancer (NSCLC) with a primary histology of squamous carcinoma who have received prior systemic therapy for advanced NSCLC will be enrolled in Part 3
Key exclusion criteria (6 listed)
- Uncontrolled brain metastasis
- Significant cardiovascular disease
- Inadequate blood counts
- Inadequate liver, kidney or lung function
- Gastrointestinal disease within last 3 months
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 |
|---|---|---|
| BMS-833923 (XL139)Capsules, Oral, 30 mg starting; dose escalation, Once daily, 37 days; additional days if receiving benefit | Drug | BMS-833923 |
Primary outcome
Use National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) to establish the maximum tolerated dose, a recommended Phase 2 dose range and schedule, and safety profile of BMS-833923
Time frame: On average a minimum of 60 days up to 3 years
Use NCI CTCAE to monitor safety assessments including physical findings, laboratory tests, and radiographic assessments to establish the maximum tolerated dose and recommended Phase 2 dose range and schedule of BMS-833923
12 secondary outcomes
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Maximum observed plasma concentration (Cmax)
Time frame: Study day 1-7, 36
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Time of maximum observed plasma concentration (Tmax)
Time frame: Study day 1-7, 36
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)] of BMS-833923 (XL139)
Time frame: Study day 1-7
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-833923 (XL139)
Time frame: Study day 1-7
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Plasma half-life (T-HALF) of BMS-833923 (XL139)
Time frame: Study day 1-7
Pharmacokinetic parameters of BMS-833923 (XL139) during daily dosing: Minimum observed plasma concentration (Cmin) of BMS-833923 (XL139)
Time frame: Study day 1, 8, 15, 22, 29, 36, 64, and 92
Pharmacokinetic parameters of BMS-833923 (XL139) during daily dosing: Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-833923 (XL139)
Time frame: Study day 36
To assess the pharmacodynamic effects of BMS-833923 (XL139) on Hedgehog (HH) pathway activation in skin by evaluation of biomarkers such as, but not limited to GLI-1 protein or mRNA expression using immunohistochemistry (IHC) or RT-PCR in a skin biopsies
Time frame: At screening (baseline) and between days 22 and 36 of treatment
To assess the pharmacodynamic effects of BMS-833923 (XL139) on HH pathway activation in subjects' tumors by evaluation of protein and mRNA of biomarkers such as, but not limited to GLI-1, in pre- and during-treatment tumor samples
Time frame: At screening (baseline) and between days 22 and 36 of treatment. At screening only for NSCLC patients
To describe any preliminary evidence of anti-tumor activity of BMS-833923 (XL139)
Time frame: Every 8 weeks until disease progression
Safety profile of multiple doses of BMS-833923
Time frame: Adverse event reports: On average a minimum of 60 days up to 3 years
Safety profile of multiple doses of BMS-833923
Time frame: Conducted at least on days 1, 8, 15, 22 and 36 of the first 36-day cycle and then monthly or biweekly for the first 6 months, then monthly
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2014.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMS-833923 (XL139) in people with Hedgehog Pathway and Smoothened, run by Bristol-Myers Squibb at 3 sites in 2 countries.
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 4 inclusion and 6 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: finished, as of the sponsor's last update on 15 Aug 2014. 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, Canada. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Use National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) to establish the maximum tolerated dose, a recommended Phase 2 dose range and schedule, and safety profile of BMS-833923 (time frame: On average a minimum of 60 days up to 3 years). 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 15 Aug 2014.