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

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT00807859

Collaborator

(none)

Enrollment

Locations

Arms

79.3

Actual Duration (Months)

2.8

Patients Per Site

Patients Per Site Per Month

Study Details

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.

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 Design

Study Type:

Interventional

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

Actual Study Start Date :

Mar 9, 2009

Actual Primary Completion Date :

Feb 27, 2014

Actual Study Completion Date :

Oct 19, 2015

Arms and Interventions

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

Outcome Measures

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 [24 months]

Secondary Outcome Measures

To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs [24 months]
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 [24 months]
To estimate the incidence of anti AMG 386 antibody formation [24 months]
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) [23 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Tucson	Arizona	United States	85724
2	Research Site	Boca Raton	Florida	United States	33428
3	Research Site	Iowa City	Iowa	United States	52242
4	Research Site	Boston	Massachusetts	United States	02111
5	Research Site	Minneapolis	Minnesota	United States	55407
6	Research Site	Lebanon	New Hampshire	United States	03756-0001
7	Research Site	Lebanon	New Hampshire	United States	03756
8	Research Site	Albuquerque	New Mexico	United States	87131
9	Research Site	Great Neck	New York	United States	11021
10	Research Site	New City	New York	United States	10956
11	Research Site	New York	New York	United States	10032
12	Research Site	Nyack	New York	United States	10960
13	Research Site	Middletown	Ohio	United States	45042
14	Research Site	Leuven		Belgium	3000
15	Research Site	Liege		Belgium	4000
16	Research Site	Wilrijk		Belgium	2610
17	Research Site	Bordeaux		France	33075
18	Research Site	Caen Cedex 05		France	14076
19	Research Site	La Roche Sur Yon Cedex 9		France	85925
20	Research Site	Marseille		France	13009
21	Research Site	Nantes Cedex 2		France	44202
22	Research Site	Pierre BÃ©nite Cedex		France	69495
23	Research Site	Toulouse		France	31052