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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Breast Cancer; Breast Neoplasms; Metastatic Cancer; Breast Tumors; Solid Tumors; Oncology; Tumors; Metastases; Locally Recurrent and Metastatic Breast Cancer
• Intervention / Treatment: Drug: AMG 386 10 mgkg, Paclitaxel and Trastuzumab; Drug: AMG 386 30 mg/kg, Paclitaxel and Trastuzumab; Drug: AMG 386 10 mg/kg, Capecitabine and Lapatinib; Drug: AMG 386 30 mg/kg, Capecitabine and Lapatinib

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Research Site
  • Liege, Belgium, 4000
    • Research Site
  • Wilrijk, Belgium, 2610
    • Research Site
• France
  • 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
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Research Site
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Research Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Research Site
    • Lebanon, New Hampshire, United States, 03756-0001
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Research Site
  • New York
    • 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
      • Research Site
  • Ohio
    • Middletown, Ohio, United States, 45042
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Kaufman PA, Wildiers H, Freyer G, Kemeny M, Goncalves 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 9, 2009
• Primary Completion (ACTUAL): February 27, 2014
• Study Completion (ACTUAL): October 19, 2015

Study Registration Dates

• First Submitted: December 11, 2008
• First Submitted That Met QC Criteria: December 11, 2008
• First Posted (ESTIMATE): December 12, 2008

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Capecitabine; Xeloda; Trastuzumab; Paclitaxel; Taxol; HER2-positive; Herceptin; Lapatinib; metastatic breast cancer; Tykerb; locally recurrent breast cancer; AMG 386; anti-angiogenic therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Breast Neoplasms; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Paclitaxel; Trastuzumab; Capecitabine; Albumin-Bound Paclitaxel; Lapatinib; Trebananib
• Other Study ID Numbers: 20062042