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

Basal Cell Carcinoma (BCC) Clinical Trial

Official title:

A Phase 1 Multiple Ascending Dose Study of BMS-833923 in Subjects With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00670189
• Other study ID #: CA194-002
• Status: Completed
• Phase: Phase 1
• First received: April 29, 2008
• Last updated: August 13, 2014
• Start date: July 2008
• Est. completion date: May 2014

Study information

• Verified date: August 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: May 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Basal Cell Carcinoma (BCC)
• Basal Cell Nevoid Syndrome (BCNS)
• Carcinoma, Basal Cell
• Hedgehog Pathway
• Smoothened

Intervention

Drug:
• BMS-833923 (XL139)
Capsules, Oral, 30 mg starting; dose escalation, Once daily, 37 days; additional days if receiving benefit

Locations

Country	Name	City	State
Canada	Local Institution	Toronto	Ontario
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Southwest Texas Addiction Research And Tech (Start) Center	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Exelixis

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	On average a minimum of 60 days up to 3 years	Yes
Secondary	Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Maximum observed plasma concentration (Cmax)		Study day 1-7, 36	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Plasma half-life (T-HALF) of BMS-833923 (XL139)		Study day 1-7	No
Secondary	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	No
Secondary	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	No
Secondary	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)	At screening (baseline) and between days 22 and 36 of treatment	No
Secondary	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)	At screening (baseline) and between days 22 and 36 of treatment. At screening only for NSCLC patients	No
Secondary	To describe any preliminary evidence of anti-tumor activity of BMS-833923 (XL139)	Tumor assessments by computed tomography (CT)	Every 8 weeks until disease progression	No
Secondary	Safety profile of multiple doses of BMS-833923	Medical review of adverse event reports	Adverse event reports: On average a minimum of 60 days up to 3 years	Yes
Secondary	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	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	Yes

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