Basal Cell Carcinoma (BCC), Basal Cell Nevoid Syndrome (BCNS), Hedgehog Pathway, Smoothened
Conditions
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
Interventions
Capsules, Oral, 30 mg starting; dose escalation, Once daily, 37 days; additional days if receiving benefit
Sponsors
Exelixis
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Time of maximum observed plasma concentration (Tmax) | 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) | 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) | Study day 1-7 | — |
| Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Plasma half-life (T-HALF) of BMS-833923 (XL139) | Study day 1-7 | — |
| Pharmacokinetic parameters of BMS-833923 (XL139) during daily dosing: Minimum observed plasma concentration (Cmin) of BMS-833923 (XL139) | Study day 1, 8, 15, 22, 29, 36, 64, and 92 | — |
| Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Maximum observed plasma concentration (Cmax) | Study day 1-7, 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 | At screening (baseline) and between days 22 and 36 of treatment | glioma-associated oncogene family of transcription factors (GLI) |
| 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 | At screening (baseline) and between days 22 and 36 of treatment. At screening only for NSCLC patients | glioma-associated oncogene family of transcription factors (GLI) |
| To describe any preliminary evidence of anti-tumor activity of BMS-833923 (XL139) | Every 8 weeks until disease progression | Tumor assessments by computed tomography (CT) |
| Safety profile of multiple doses of BMS-833923 | Adverse event reports: On average a minimum of 60 days up to 3 years | Medical review of adverse event reports |
| 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) | Study day 36 | — |
Countries
Canada, United States
Outcome results
None listed