Safety Study of AMG 386 to Treat HER2-Positive Locally Recurrent or Metastatic Breast Cancer - Full Text View

Sponsored by:	Amgen
Information provided by:	Amgen
ClinicalTrials.gov Identifier:	NCT00807859

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 de-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 dose 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 10 mgkg, Paclitaxel and Trastuzumab Drug: AMG 386 3 mg/kg, Paclitaxel and Trastuzumab Drug: AMG 386 10 mg/kg, Capecitabine and Lapatinib Drug: AMG 386 3 mg/kg, Capecitabine and Lapatinib	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Paclitaxel Capecitabine Trastuzumab Lapatinib Lapatinib Ditosylate AMG 386

U.S. FDA Resources

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 ]

Estimated Enrollment:	40
Study Start Date:	December 2008
Estimated Study Completion Date:	March 2012
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Cohort A1: Experimental	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
Cohort B2: Experimental	Drug: AMG 386 3 mg/kg, Capecitabine and Lapatinib AMG 386 3 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 B1: Experimental	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
Cohort A2: Experimental	Drug: AMG 386 3 mg/kg, Paclitaxel and Trastuzumab AMG 386 3 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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects must have histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection 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:
Subjects must be either trastuzumab naïve or have had prior trastuzumab in the adjuvant setting only
Subjects must not have had a clinically significant drop in cardiac function during a prior exposure to trastuzumab
Subjects must have had 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:
Subjects must have failed (due to disease progression or toxicity) trastuzumab in the first-line metastatic setting. Trastuzumab must be discontinued for at least 3 weeks prior to enrollment
Subjects 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
Subjects must have had no prior capecitabine
Subjects must have had no prior lapatinib

Exclusion Criteria:

Inflammatory breast cancer
Current or prior history of central nervous system metastasis
Clinically significant cardiovascular disease
Concurrent or prior (within 1 week before enrollment) anticoagulation therapy, excluding aspirin and anti-platelet agents. The concurrent use of low molecular weight heparin or low dose warfarin (ie, less than or equal to 1 mg daily) for prophylaxis against thrombosis is acceptable while on study
Subjects with a history of prior malignancy, except:
Malignancy treated with curative intent and with no known active disease present for greater than or equal to 3 years before enrollment and felt to be at low risk for recurrence by treating physician
Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease
Adequately treated cervical carcinoma in situ without evidence of disease
Subjects with interstitial pulmonary disease
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00807859

Contacts

Contact: Amgen Call Center

866-572-6436

Locations

United States, Arizona
Research Site	Recruiting
Tucson, Arizona, United States
United States, Florida
Research Site	Recruiting
Boca Raton, Florida, United States
United States, Ohio
Research Site	Recruiting
Middletown, Ohio, United States

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Amgen Inc. ( Global Development Leader )
Study ID Numbers:	20062042
Study First Received:	December 11, 2008
Last Updated:	June 18, 2009
ClinicalTrials.gov Identifier:	NCT00807859 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board; United States: Western Institutional Review Board

Keywords provided by Amgen:

AMG 386
Paclitaxel
Trastuzumab
Capecitabine
Lapatinib
HER2-positive
metastatic breast cancer

locally recurrent breast cancer
Taxol
Herceptin
Xeloda
Tykerb
anti-angiogenic therapy

Study placed in the following topic categories:

Antimetabolites
Capecitabine
Skin Diseases
Breast Neoplasms
Lapatinib
Antimitotic Agents
Protein Kinase Inhibitors
Angiogenesis Inhibitors

Recurrence
Paclitaxel
Tubulin Modulators
Neoplasm Metastasis
Trastuzumab
Antineoplastic Agents, Phytogenic
Breast Diseases

Additional relevant MeSH terms:

Antimetabolites
Disease Attributes
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Therapeutic Uses
Trastuzumab
Neoplasm Metastasis
Breast Diseases

Capecitabine
Skin Diseases
Mitosis Modulators
Breast Neoplasms
Enzyme Inhibitors
Lapatinib
Antimitotic Agents
Recurrence
Pharmacologic Actions
Neoplasms
Paclitaxel
Tubulin Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 06, 2009