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

Phase 1

Completed

• Conditions: Hedgehog Pathway; Smoothened; Basal Cell Carcinoma (BCC); Basal Cell Nevoid Syndrome (BCNS)
• Interventions: Drug: BMS-833923 (XL139)

• Registration Number: NCT00670189
• Lead Sponsor: Bristol-Myers Squibb

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

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2008-04-29
• Study First Submitted QC: 2008-04-29
• Study First Posted: 2008-05-01
• Study Start: 2008-07
• Primary Completion: 2014-04
• Study Completion: 2014-05
• Status Verified: 2014-08
• Last Update Submitted: 2014-08-13
• Last Update Posted: 2014-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BMS-833923	BMS-833923 (XL139)	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Maximum observed plasma concentration (Cmax)	Study day 1-7, 36
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
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)
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) during daily dosing: Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-833923 (XL139)	Study day 36
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	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	The results of vital sign measurements, electrocardiogram (ECGs), pulmonary function tests, multigated radionuclide angiography (MUGA) or echocardiograms, physical examinations, and clinical laboratory tests

Trial Locations

Locations (3)

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

Southwest Texas Addiction Research And Tech (Start) Center; 🇺🇸 San Antonio, Texas, United States

Local Institution; 🇨🇦 Toronto, Ontario, Canada