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

NCT ID: NCT00807859

Last Updated: 2022-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-09

Study Completion Date

2015-10-19

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Cancer Breast Neoplasms Breast Tumors Cancer Locally Recurrent and Metastatic Breast Cancer Metastases Metastatic Cancer Oncology Solid Tumors Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A1

Group Type EXPERIMENTAL

AMG 386 10 mgkg, Paclitaxel and Trastuzumab

Intervention Type DRUG

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

Cohort A3

Group Type EXPERIMENTAL

AMG 386 30 mg/kg, Paclitaxel and Trastuzumab

Intervention Type DRUG

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

Cohort B1

Group Type EXPERIMENTAL

AMG 386 10 mg/kg, Capecitabine and Lapatinib

Intervention Type DRUG

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

Cohort B3

Group Type EXPERIMENTAL

AMG 386 30 mg/kg, Capecitabine and Lapatinib

Intervention Type DRUG

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

Interventions

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AMG 386 30 mg/kg, Paclitaxel and Trastuzumab

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

AMG 386 30 mg/kg, Capecitabine and Lapatinib

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

AMG 386 10 mgkg, Paclitaxel and Trastuzumab

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

AMG 386 10 mg/kg, Capecitabine and Lapatinib

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

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Tucson, Arizona, United States

Site Status

Research Site

Boca Raton, Florida, United States

Site Status

Research Site

Iowa City, Iowa, United States

Site Status

Research Site

Boston, Massachusetts, United States

Site Status

Research Site

Minneapolis, Minnesota, United States

Site Status

Research Site

Lebanon, New Hampshire, United States

Site Status

Research Site

Lebanon, New Hampshire, United States

Site Status

Research Site

Albuquerque, New Mexico, United States

Site Status

Research Site

Great Neck, New York, United States

Site Status

Research Site

New City, New York, United States

Site Status

Research Site

New York, New York, United States

Site Status

Research Site

Nyack, New York, United States

Site Status

Research Site

Middletown, Ohio, United States

Site Status

Research Site

Leuven, , Belgium

Site Status

Research Site

Liège, , Belgium

Site Status

Research Site

Wilrijk, , Belgium

Site Status

Research Site

Bordeaux, , France

Site Status

Research Site

Caen, , France

Site Status

Research Site

La Roche-sur-Yon, , France

Site Status

Research Site

Marseille, , France

Site Status

Research Site

Nantes, , France

Site Status

Research Site

Pierre Bénite Cedex, , France

Site Status

Research Site

Toulouse, , France

Site Status

Countries

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United States Belgium France

References

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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.

Reference Type BACKGROUND
PMID: 30420181 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20062042

Identifier Type: -

Identifier Source: org_study_id

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