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

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

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

Study Overview

• Status: Completed
• Conditions: Basal Cell Carcinoma (BCC); Hedgehog Pathway; Smoothened; Basal Cell Nevoid Syndrome (BCNS)
• Intervention / Treatment: Drug: BMS-833923 (XL139)

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Texas
    • San Antonio, Texas, United States, 78229
      • Southwest Texas Addiction Research And Tech (Start) Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BMS-833923	Drug: BMS-833923 (XL139); Capsules, Oral, 30 mg starting; dose escalation, Once daily, 37 days; additional days if receiving benefit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 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
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
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
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
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Exelixis

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (ACTUAL): April 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: April 29, 2008
• First Submitted That Met QC Criteria: April 29, 2008
• First Posted (ESTIMATE): May 1, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): August 15, 2014
• Last Update Submitted That Met QC Criteria: August 13, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Basal Cell; Carcinoma, Basal Cell
• Other Study ID Numbers: CA194-002