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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Exelixis
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00670189
First received: April 29, 2008
Last updated: August 22, 2013
Last verified: August 2013
  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:


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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00670189

Locations
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Texas
Southwest Texas Addiction Research And Tech (Start) Center
San Antonio, Texas, United States, 78229
Canada, Ontario
Local Institution
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Bristol-Myers Squibb
Exelixis
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
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: August 22, 2013
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 July 28, 2014