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

Primary Purpose

Hedgehog Pathway, Smoothened, Basal Cell Carcinoma (BCC)

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BMS-833923 (XL139)
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hedgehog Pathway

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic Rochester
  • Southwest Texas Addiction Research And Tech (Start) Center
  • Local Institution

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BMS-833923

Arm Description

Outcomes

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
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)
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Time of maximum observed plasma concentration (Tmax)
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)
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)
Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Plasma half-life (T-HALF) of BMS-833923 (XL139)
Pharmacokinetic parameters of BMS-833923 (XL139) during daily dosing: Minimum observed plasma concentration (Cmin) of BMS-833923 (XL139)
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)
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)
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)
To describe any preliminary evidence of anti-tumor activity of BMS-833923 (XL139)
Tumor assessments by computed tomography (CT)
Safety profile of multiple doses of BMS-833923
Medical review of adverse event reports
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

Full Information

First Posted
April 29, 2008
Last Updated
August 13, 2014
Sponsor
Bristol-Myers Squibb
Collaborators
Exelixis
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1. Study Identification

Unique Protocol Identification Number
NCT00670189
Brief Title
A Phase 1 Study of BMS-833923 (XL139) in Subjects With Advanced or Metastatic Cancer
Official Title
A Phase 1 Multiple Ascending Dose Study of BMS-833923 in Subjects With Advanced or Metastatic Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
Collaborators
Exelixis

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hedgehog Pathway, Smoothened, Basal Cell Carcinoma (BCC), Basal Cell Nevoid Syndrome (BCNS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BMS-833923
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BMS-833923 (XL139)
Intervention Description
Capsules, Oral, 30 mg starting; dose escalation, Once daily, 37 days; additional days if receiving benefit
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
On average a minimum of 60 days up to 3 years
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Description
glioma-associated oncogene family of transcription factors (GLI)
Time Frame
At screening (baseline) and between days 22 and 36 of treatment
Title
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
Description
glioma-associated oncogene family of transcription factors (GLI)
Time Frame
At screening (baseline) and between days 22 and 36 of treatment. At screening only for NSCLC patients
Title
To describe any preliminary evidence of anti-tumor activity of BMS-833923 (XL139)
Description
Tumor assessments by computed tomography (CT)
Time Frame
Every 8 weeks until disease progression
Title
Safety profile of multiple doses of BMS-833923
Description
Medical review of adverse event reports
Time Frame
Adverse event reports: On average a minimum of 60 days up to 3 years
Title
Safety profile of multiple doses of BMS-833923
Description
The results of vital sign measurements, electrocardiogram (ECGs), pulmonary function tests, multigated radionuclide angiography (MUGA) or echocardiograms, physical examinations, and clinical laboratory tests
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Southwest Texas Addiction Research And Tech (Start) Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Local Institution
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource

Learn more about this trial

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

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