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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00807859
• Other study ID #: 20062042
• Status: Completed
• Phase: Phase 1
• Start date: March 9, 2009
• Est. completion date: October 19, 2015

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: October 19, 2015
• Est. primary completion date: February 27, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

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
• 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
• 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
• 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

Locations

Country	Name	City	State
Belgium	Research Site	Leuven
Belgium	Research Site	Liege
Belgium	Research Site	Wilrijk
France	Research Site	Bordeaux
France	Research Site	Caen Cedex 05
France	Research Site	La Roche Sur Yon Cedex 9
France	Research Site	Marseille
France	Research Site	Nantes Cedex 2
France	Research Site	Pierre Bénite Cedex
France	Research Site	Toulouse
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Boca Raton	Florida
United States	Research Site	Boston	Massachusetts
United States	Research Site	Great Neck	New York
United States	Research Site	Iowa City	Iowa
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Middletown	Ohio
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	New City	New York
United States	Research Site	New York	New York
United States	Research Site	Nyack	New York
United States	Research Site	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Belgium,  France, 

References & Publications (1)

Kaufman PA, Wildiers H, Freyer G, Kemeny M, Gonçalves 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs		24 months
Secondary	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
Secondary	To estimate the incidence of anti AMG 386 antibody formation		24 months
Secondary	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

External Links

•   AmgenTrials clinical trials website