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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00807859
Recruitment Status : Completed
First Posted : December 12, 2008
Last Update Posted : November 2, 2015
Sponsor:
Information provided by (Responsible Party):
Amgen

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Breast Neoplasms Breast Tumors Cancer Locally Recurrent and Metastatic Breast Cancer Metastases Metastatic Cancer Oncology Solid Tumors Tumors Drug: AMG 386 30 mg/kg, Paclitaxel and Trastuzumab Drug: AMG 386 30 mg/kg, Capecitabine and Lapatinib Drug: AMG 386 10 mgkg, Paclitaxel and Trastuzumab Drug: AMG 386 10 mg/kg, Capecitabine and Lapatinib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : March 2009
Primary Completion Date : February 2014
Study Completion Date : October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Cohort A1 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
Experimental: Cohort A3 Drug: 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
Experimental: Cohort B1 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
Experimental: Cohort B3 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



Primary Outcome Measures :
  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 [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs [ Time Frame: 24 months ]
  2. 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 ]
  3. To estimate the incidence of anti AMG 386 antibody formation [ Time Frame: 24 months ]
  4. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00807859


Locations
United States, Arizona
Research Site
Tucson, Arizona, United States, 85724
United States, Florida
Research Site
Boca Raton, Florida, United States, 33428
United States, Iowa
Research Site
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02111
United States, Minnesota
Research Site
Minneapolis, Minnesota, United States, 55407
United States, New Hampshire
Research Site
Lebanon, New Hampshire, United States, 03756-0001
Research Site
Lebanon, New Hampshire, United States, 03756
United States, New Mexico
Research Site
Albuquerque, New Mexico, United States, 87131
United States, New York
Research Site
Great Neck, New York, United States, 11021
Research Site
New City, New York, United States, 10956
Research Site
New York, New York, United States, 10032
Research Site
Nyack, New York, United States, 10960
United States, Ohio
Research Site
Middletown, Ohio, United States, 45042
Belgium
Research Site
Leuven, Belgium, 3000
Research Site
Liege, Belgium, 4000
Research Site
Wilrijk, Belgium, 2610
France
Research Site
Bordeaux, France, 33075
Research Site
Caen Cedex 05, France, 14076
Research Site
La Roche Sur Yon Cedex 9, France, 85925
Research Site
Marseille, France, 13009
Research Site
Nantes Cedex 2, France, 44202
Research Site
Pierre Bénite Cedex, France, 69495
Research Site
Toulouse, France, 31052
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00807859     History of Changes
Other Study ID Numbers: 20062042
First Posted: December 12, 2008    Key Record Dates
Last Update Posted: November 2, 2015
Last Verified: October 2015

Keywords provided by Amgen:
metastatic breast cancer
locally recurrent breast cancer
AMG 386
Paclitaxel
Trastuzumab
Capecitabine
Lapatinib
HER2-positive
Taxol
Herceptin
Xeloda
Tykerb
anti-angiogenic therapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Paclitaxel
Lapatinib
Trebananib
Albumin-Bound Paclitaxel
Capecitabine
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Protein Kinase Inhibitors
Enzyme Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors