Clinical trial NCT00670189: A Phase 1 Study of BMS-833923 (XL139) in Subjects With Advanced or Metastatic Cancer
Official title: A Phase 1 Multiple Ascending Dose Study of BMS-833923 in Subjects With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hedgehog Pathway
Smoothened
Basal Cell Carcinoma (BCC)
Basal Cell Nevoid Syndrome (BCNS)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Exelixis
First posted: 2008-05-01
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation.

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
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
timeFrame: On average a minimum of 60 days up to 3 years
Secondary outcomes:
measure: Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Maximum observed plasma concentration (Cmax)
timeFrame: Study day 1-7, 36
measure: Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Time of maximum observed plasma concentration (Tmax)
timeFrame: Study day 1-7, 36
measure: 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)
timeFrame: Study day 1-7
measure: 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)
timeFrame: Study day 1-7
measure: Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Plasma half-life (T-HALF) of BMS-833923 (XL139)
timeFrame: Study day 1-7
measure: Pharmacokinetic parameters of BMS-833923 (XL139) during daily dosing: Minimum observed plasma concentration (Cmin) of BMS-833923 (XL139)
timeFrame: Study day 1, 8, 15, 22, 29, 36, 64, and 92
measure: 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)
timeFrame: Study day 36
measure: 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
timeFrame: At screening (baseline) and between days 22 and 36 of treatment
measure: 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
timeFrame: At screening (baseline) and between days 22 and 36 of treatment. At screening only for NSCLC patients
measure: To describe any preliminary evidence of anti-tumor activity of BMS-833923 (XL139)
timeFrame: Every 8 weeks until disease progression
measure: Safety profile of multiple doses of BMS-833923
timeFrame: Adverse event reports: On average a minimum of 60 days up to 3 years
measure: Safety profile of multiple doses of BMS-833923
timeFrame: 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
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: San Antonio
country: United States
facility: Southwest Texas Addiction Research And Tech (Start) Center
state: Texas
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: