search
Back to results

Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer

Primary Purpose

Breast Cancer, Breast Neoplasms, Breast Tumors

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AMG 386 30 mg/kg, Paclitaxel and Trastuzumab
AMG 386 30 mg/kg, Capecitabine and Lapatinib
AMG 386 10 mgkg, Paclitaxel and Trastuzumab
AMG 386 10 mg/kg, Capecitabine and Lapatinib
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring AMG 386, Paclitaxel, Trastuzumab, Capecitabine, Lapatinib, HER2-positive, metastatic breast cancer, locally recurrent breast cancer, Taxol, Herceptin, Xeloda, Tykerb, anti-angiogenic therapy

Eligibility Criteria

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

Inclusion Criteria:

  • 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
  • Must have received prior chemotherapy as adjuvant therapy or for metastatic disease
  • Prior chemotherapy treatment must be discontinued for at least 3 weeks prior to enrollment
  • No prior capecitabine
  • No prior lapatinib

Exclusion Criteria:

  • 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)

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort A1

Cohort A3

Cohort B1

Cohort B3

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs
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
To estimate the incidence of anti AMG 386 antibody formation
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)

Full Information

First Posted
December 11, 2008
Last Updated
November 4, 2022
Sponsor
Amgen
search

1. Study Identification

Unique Protocol Identification Number
NCT00807859
Brief Title
Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
March 9, 2009 (Actual)
Primary Completion Date
February 27, 2014 (Actual)
Study Completion Date
October 19, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Breast Neoplasms, Breast Tumors, Cancer, Locally Recurrent and Metastatic Breast Cancer, Metastases, Metastatic Cancer, Oncology, Solid Tumors, Tumors
Keywords
AMG 386, Paclitaxel, Trastuzumab, Capecitabine, Lapatinib, HER2-positive, metastatic breast cancer, locally recurrent breast cancer, Taxol, Herceptin, Xeloda, Tykerb, anti-angiogenic therapy

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Cohort A1
Arm Type
Experimental
Arm Title
Cohort A3
Arm Type
Experimental
Arm Title
Cohort B1
Arm Type
Experimental
Arm Title
Cohort B3
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AMG 386 30 mg/kg, Paclitaxel and Trastuzumab
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
AMG 386 30 mg/kg, Capecitabine and Lapatinib
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
AMG 386 10 mgkg, Paclitaxel and Trastuzumab
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
AMG 386 10 mg/kg, Capecitabine and Lapatinib
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Time Frame
24 months
Secondary Outcome Measure Information:
Title
To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs
Time Frame
24 months
Title
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
Time Frame
24 months
Title
To estimate the incidence of anti AMG 386 antibody formation
Time Frame
24 months
Title
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)
Time Frame
23 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Must have received prior chemotherapy as adjuvant therapy or for metastatic disease Prior chemotherapy treatment must be discontinued for at least 3 weeks prior to enrollment No prior capecitabine No prior lapatinib Exclusion Criteria: 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Research Site
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33428
Country
United States
Facility Name
Research Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Research Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Research Site
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756-0001
Country
United States
Facility Name
Research Site
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Research Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Research Site
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
Research Site
City
New City
State/Province
New York
ZIP/Postal Code
10956
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Research Site
City
Nyack
State/Province
New York
ZIP/Postal Code
10960
Country
United States
Facility Name
Research Site
City
Middletown
State/Province
Ohio
ZIP/Postal Code
45042
Country
United States
Facility Name
Research Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Research Site
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Research Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Research Site
City
Bordeaux
ZIP/Postal Code
33075
Country
France
Facility Name
Research Site
City
Caen Cedex 05
ZIP/Postal Code
14076
Country
France
Facility Name
Research Site
City
La Roche Sur Yon Cedex 9
ZIP/Postal Code
85925
Country
France
Facility Name
Research Site
City
Marseille
ZIP/Postal Code
13009
Country
France
Facility Name
Research Site
City
Nantes Cedex 2
ZIP/Postal Code
44202
Country
France
Facility Name
Research Site
City
Pierre Bénite Cedex
ZIP/Postal Code
69495
Country
France
Facility Name
Research Site
City
Toulouse
ZIP/Postal Code
31052
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
30420181
Citation
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.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer

We'll reach out to this number within 24 hrs