A Phase 1 Study of BMS-833923 (XL139) in Subjects With Advanced or Metastatic Cancer
This study is ongoing, but not recruiting participants.
Sponsor:
Bristol-Myers Squibb
Collaborator:
Exelixis
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00670189
First received: April 29, 2008
Last updated: July 3, 2012
Last verified: July 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Hedgehog Pathway Smoothened Basal Cell Carcinoma (BCC) Basal Cell Nevoid Syndrome (BCNS) |
Drug: BMS-833923 (XL139) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 1 Multiple Ascending Dose Study of BMS-833923 in Subjects With Advanced or Metastatic Solid Tumors |
Resource links provided by NLM:
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: Yes ]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 Outcome Measures:
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]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 [ Time Frame: At screening (baseline) and between days 22 and 36 of treatment. At screening only for NSCLC patients ] [ Designated as safety issue: No ]glioma-associated oncogene family of transcription factors (GLI)
- To describe any preliminary evidence of anti-tumor activity of BMS-833923 (XL139) [ Time Frame: Every 8 weeks until disease progression ] [ Designated as safety issue: No ]Tumor assessments by computed tomography (CT)
- Safety profile of multiple doses of BMS-833923 [ Time Frame: Adverse event reports: On average a minimum of 60 days up to 3 years ] [ Designated as safety issue: Yes ]Medical review of adverse event reports
- 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 ] [ Designated as safety issue: Yes ]The results of vital sign measurements, electrocardiogram (ECGs), pulmonary function tests, multigated radionuclide angiography (MUGA) or echocardiograms, physical examinations, and clinical laboratory tests
| Estimated Enrollment: | 70 |
| Study Start Date: | July 2008 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: BMS-833923 |
Drug: BMS-833923 (XL139)
Capsules, Oral, 30 mg starting; dose escalation, Once daily, 37 days; additional days if receiving benefit
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00670189
Locations
| United States, Minnesota | |
| Mayo Clinic Rochester | |
| Rochester, Minnesota, United States, 55905 | |
| United States, New York | |
| Local Institution | |
| New York, New York, United States, 10021 | |
| United States, Texas | |
| Local Institution | |
| Dallas, Texas, United States, 75230 | |
| South Texas Accelerated Research Therapeutics | |
| San Antonio, Texas, United States, 78229 | |
| Canada, Alberta | |
| Local Institution | |
| Edmonton, Alberta, Canada, T6G 1Z2 | |
| Canada, Ontario | |
| Local Institution | |
| Toronto, Ontario, Canada, M5G 2M9 | |
Sponsors and Collaborators
Bristol-Myers Squibb
Exelixis
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT00670189 History of Changes |
| Other Study ID Numbers: | CA194-002 |
| Study First Received: | April 29, 2008 |
| Last Updated: | July 3, 2012 |
| Health Authority: | United States: Food and Drug Administration Canada: Health Canada |
Additional relevant MeSH terms:
|
Carcinoma Carcinoma, Basal Cell Neoplasms, Glandular and Epithelial |
Neoplasms by Histologic Type Neoplasms Neoplasms, Basal Cell |
ClinicalTrials.gov processed this record on May 23, 2013