Combination Study of BMS-754807 and Herceptin® in Patients With Advanced or Metastatic Her-2-positive Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00788333
First received: November 7, 2008
Last updated: July 12, 2012
Last verified: July 2012
  Purpose

This is a Phase I/II study to evaluate the safety profile, tolerability, pharmacokinetics and pharmacodynamics following daily oral doses of 50 to 200 mg of BMS-754807 in combination with trastuzumab (Herceptin®) in subjects with advanced or metastatic Her-2-positive breast cancer. In addition, the study is expected to identify the recommended dose or dose range of BMS-754807 in combination with trastuzumab for Phase II studies and provide preliminary evidence of anti-tumor activity in Her-2-positive breast cancer subjects after trastuzumab failure


Condition Intervention Phase
Breast Cancer
Drug: BMS-754807
Drug: trastuzumab (Herceptin®)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of BMS-754807 in Combination With Trastuzumab (Herceptin®) in Subjects With Advanced or Metastatic Her-2-positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • The dose escalation portion will determine the MTD and recommended Phase 2 dose or dose range of BMS-754807 when administered orally on a daily schedule in combination with trastuzumab administered at standard doses IV on a weekly basis [ Time Frame: Every 30 days until MTD is reached ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess anti-tumor activity of combination at MTD of BMS-754807 (dose expansion cohort) [ Time Frame: Every 8 weeks ] [ Designated as safety issue: Yes ]
  • Evaluate safety and tolerability of the combination regimen [ Time Frame: Ongoing ] [ Designated as safety issue: Yes ]
  • Assess effect of combination therapy on glucose metabolism [ Time Frame: At 30 days, then every 8 weeks ] [ Designated as safety issue: Yes ]
  • Explore whether co-medication with oral anti-hyperglycemic agent can enable adequate tolerability of the combination therapy if BMS-754807 induces hyperglycemia [ Time Frame: Ongoing ] [ Designated as safety issue: Yes ]
  • Obtain BMS-754807 plasma concentrations vs time data for future population PK analysis [ Time Frame: Days, 1,8,15,22 ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: July 2009
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Combination
Drug: BMS-754807
Tablets, Oral, Dose escalation to MTD, then MTD to response/EOT, once daily, Varies - treatment is continued to disease progression or MD/subject/Sponsor decision to stop
Other Name: IGF-IR
Drug: trastuzumab (Herceptin®)
IV solution, IV, 4mg/kg Day 1 loading dose, 2mg/kg once weekly, Varies - treatment is continued to disease progression or MD/subject/Sponsor decision to stop
Other Name: Herceptin®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

For additional information on this trial, please call (910) 558-2913

Inclusion Criteria:

  • Subjects with locally advanced or metastatic Her-2-positive breast cancer who have failed at least one trastuzumab containing regimen. Prior treatment with other Her-2-targeted agents (e.g. lapatinib, pertuzumab, trastuzumab DM-1 etc.) is allowed
  • Histologic or cytologic diagnosis of Her-2-positive breast cancer
  • ECOG status 0 - 1

Exclusion Criteria:

  • Symptomatic brain metastasis
  • Any condition requiring chronic use of steroids
  • Any disorder with dysregulation of glucose homeostasis (history of Type 1 or 2 Diabetes Mellitus or prediabetic symptoms
  • History of glucose intolerance
  • Women of child-bearing potential unwilling or unable to use acceptable contraception methods
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00788333

Locations
Australia, South Australia
Local Institution
Kurralta Park, South Australia, Australia, 5037
Australia, Victoria
Local Institution
Frankston, Victoria, Australia, 3199
Local Institution
Geelong, Victoria, Australia, 3220
Belgium
Local Institution
Brussels, Belgium, 1000
Canada, Ontario
Local Institution
Ottawa, Ontario, Canada, K1H 8L6
Local Institution
Toronto, Ontario, Canada, M5G 1X5
Hungary
Local Institution
Budapest, Hungary, 1122
Local Institution
Miskolc, Hungary, 3526
United Kingdom
Local Institution
Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00788333     History of Changes
Other Study ID Numbers: CA191-004, EUDRACT #: 2009-013766-78
Study First Received: November 7, 2008
Last Updated: July 12, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Ministry of Health & Long Term Care, Ontario
Hungary: Ministry of Health
United Kingdom: National Institute for Health and Clinical Excellence

Keywords provided by Bristol-Myers Squibb:
Advanced or Metastatic Her-2-positive Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014