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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00807859
First received: December 11, 2008
Last updated: October 6, 2014
Last verified: September 2014
  Purpose

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 Intervention 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
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

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 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • To estimate the incidence of anti AMG 386 antibody formation [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 65
Study Start Date: March 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Research Site
Lebanon, New Hampshire, United States, 03756-0001
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
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00807859     History of Changes
Other Study ID Numbers: 20062042
Study First Received: December 11, 2008
Last Updated: October 6, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Western Institutional Review Board

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:
Neoplasm Metastasis
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Neoplastic Processes
Pathologic Processes
Skin Diseases
Paclitaxel
Lapatinib
Capecitabine
Trastuzumab
Fluorouracil
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014