A Phase 1 Study of BMS-833923 (XL139) in Subjects With Advanced or Metastatic Cancer - Full Text View

Sponsor:	Bristol-Myers Squibb
Collaborator:	Exelixis
Information provided by (Responsible Party):	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00670189

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:

MedlinePlus related topics: Cancer

U.S. FDA Resources

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

Contacts

Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email:		Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations

United States, Minnesota
Mayo Clinic Rochester	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Steven Alberts, Site 003 507-538-7623
United States, New York
Local Institution	Not yet recruiting
New York, New York, United States, 10021
Contact: Site 006
United States, Texas
Local Institution	Not yet recruiting
Dallas, Texas, United States, 75230
Contact: Site 005
South Texas Accelerated Research Therapeutics	Recruiting
San Antonio, Texas, United States, 78229
Contact: Kyriakos Papadopoulos, Site 002
Canada, Alberta
Local Institution	Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Site 007
Canada, Ontario
Local Institution	Active, not recruiting
Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

Bristol-Myers Squibb

Exelixis

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

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:	April 30, 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, 2012