Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer
An Open-Label Study of AMG 386 in Combination With Either Paclitaxel and Trastuzumab or Capecitabine and Lapatinib in Subjects With HER2-positive Locally Recurrent or Metastatic Breast Cancer
1 other identifier
interventional
65
3 countries
23
Brief Summary
The purpose of this study is to determine if AMG 386 in combination with either paclitaxel and trastuzumab or capecitabine and lapatinib is safe and well tolerated in subjects with HER2-positive locally recurrent or metastatic breast cancer. This is an open-label phase 1b trial and has 2 study parts. Study part 1 is a dose escalation study to determine a tolerable dose of AMG 386 in combination with paclitaxel and trastuzumab (cohort A) or with capecitabine and lapatinib (cohort B). Study part 2 is cohort expansion of the tolerable doses determined in part 1.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 breast-cancer
Started Mar 2009
Longer than P75 for phase_1 breast-cancer
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 11, 2008
CompletedFirst Posted
Study publicly available on registry
December 12, 2008
CompletedStudy Start
First participant enrolled
March 9, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 27, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
October 19, 2015
CompletedNovember 8, 2022
November 1, 2022
5 years
December 11, 2008
November 4, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Primary objective is to identify the incidence of adverse events and clinical laboratory abnormalities defined as a dose limiting toxicity in subjects treated with AMG 386 plus paclitaxel and trastuzumab or with AMG 386 plus capecitabine and lapatinib
24 months
Secondary Outcomes (4)
To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs
24 months
To evaluate the pharmacokinetics (PK) of AMG 386, trastuzumab, and paclitaxel (cohort A) or AMG 386, lapatinib, and capecitabine (and its active metabolite, 5-FU; cohort B) when administered in combination
24 months
To estimate the incidence of anti AMG 386 antibody formation
24 months
To evaluate the treatment effect as measured by the following: objective response rate (ORR), duration of response (DOR), change in tumor burden and progression-free survival (PFS)
23 months
Study Arms (4)
Cohort A1
EXPERIMENTALCohort A3
EXPERIMENTALCohort B1
EXPERIMENTALCohort B3
EXPERIMENTALInterventions
AMG 386 30 mg/kg IV QW, paclitaxel 80 mg/m2 IV QW, trastuzumab: initial dose 8 mg/kg IV week 1, then 6 mg/kg IV Q3W
AMG 386 30 mg/kg IV QW, capecitabine 2000 mg/m2 divided into 2 doses given PO Q12 hrs, days 1-14 every 21 days, lapatinib 1250 mg PO QD
AMG 386 10 mg/kg IV QW, paclitaxel 80 mg/m2 IV QW, trastuzumab: initial dose 8 mg/kg IV week 1, then 6 mg/kg IV Q3W
AMG 386 10 mg/kg IV QW, capecitabine 2000 mg/m2 divided into 2 doses given PO Q12 hrs, days 1-14 every 21 days, lapatinib 1250 mg PO QD
Eligibility Criteria
You may qualify if:
- histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease not amenable to any local treatment with curative intent.
- HER2-positive by FISH, CISH, or IHC 3+
- ECOG performance status 0 or 1
- Left ventricular ejection fraction greater than or equal to institutional lower limit of normal
- Adequate laboratory studies (hematological, chemistries and urinalysis)
- Life expectancy greater than or equal to 3 months
- Cohort A only:
- Trastuzumab naïve or trastuzumab in the neo-adjuvant setting
- No clinically significant drop in cardiac function prior exposure to trastuzumab
- No prior chemotherapy for metastatic or locally recurrent breast cancer
- No prior lapatinib therapy
- At least 3 weeks from enrollment since prior chemotherapeutic agents, including taxanes, in the neoadjuvant or adjuvant setting
- At least 3 months from enrollment since prior trastuzumab in the neoadjuvant or adjuvant setting
- Cohort B only:
- Must have failed trastuzumab in the first-line metastatic setting. Trastuzumab must be discontinued for at least 3 weeks prior to enrollment
- +4 more criteria
You may not qualify if:
- Inflammatory breast cancer
- Central nervous system metastasis
- Clinically significant cardiovascular disease
- Radiation therapy ≤ 14 days prior to enrollment.
- Concurrent anticoagulation therapy, excluding aspirin, anti-platelet agents, low molecular weight heparin or low dose warfarin per protocol.
- Uncontrolled hypertension defined as diastolic blood pressure \> 90 mmHg OR systolic blood pressure \> 140 mmHg.
- Subjects with a history of prior malignancy, except:
- For Cohort B only:
- Current or prior history of long QT syndrome
- Baseline ECG report of QTc interval of \> 480 milliseconds
- Severe chronic liver disease (Child Pugh C)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (23)
Research Site
Tucson, Arizona, 85724, United States
Research Site
Boca Raton, Florida, 33428, United States
Research Site
Iowa City, Iowa, 52242, United States
Research Site
Boston, Massachusetts, 02111, United States
Research Site
Minneapolis, Minnesota, 55407, United States
Research Site
Lebanon, New Hampshire, 03756-0001, United States
Research Site
Lebanon, New Hampshire, 03756, United States
Research Site
Albuquerque, New Mexico, 87131, United States
Research Site
Great Neck, New York, 11021, United States
Research Site
New City, New York, 10956, United States
Research Site
New York, New York, 10032, United States
Research Site
Nyack, New York, 10960, United States
Research Site
Middletown, Ohio, 45042, United States
Research Site
Leuven, 3000, Belgium
Research Site
Liège, 4000, Belgium
Research Site
Wilrijk, 2610, Belgium
Research Site
Bordeaux, 33075, France
Research Site
Caen, 14076, France
Research Site
La Roche-sur-Yon, 85925, France
Research Site
Marseille, 13009, France
Research Site
Nantes, 44202, France
Research Site
Pierre Bénite Cedex, 69495, France
Research Site
Toulouse, 31052, France
Related Publications (1)
Kaufman PA, Wildiers H, Freyer G, Kemeny M, Goncalves A, Jerusalem G, Stopeck A, Vrindavanam N, Dalenc F, Nanayakkara N, Wu B, Pickett CA. Phase 1b Study of Trebananib Plus Paclitaxel and Trastuzumab in Patients With HER2-Positive Locally Recurrent or Metastatic Breast Cancer. Clin Breast Cancer. 2019 Feb;19(1):47-57. doi: 10.1016/j.clbc.2018.09.012. Epub 2018 Oct 9.
PMID: 30420181BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
MD
Amgen
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 11, 2008
First Posted
December 12, 2008
Study Start
March 9, 2009
Primary Completion
February 27, 2014
Study Completion
October 19, 2015
Last Updated
November 8, 2022
Record last verified: 2022-11