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

December 11, 2008
October 6, 2014
March 2009
November 2014   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00807859 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
  • 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
  • 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
  • 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 A1
    Intervention: Drug: AMG 386 10 mgkg, Paclitaxel and Trastuzumab
  • Experimental: Cohort A3
    Intervention: Drug: AMG 386 30 mg/kg, Paclitaxel and Trastuzumab
  • Experimental: Cohort B1
    Intervention: Drug: AMG 386 10 mg/kg, Capecitabine and Lapatinib
  • Experimental: Cohort B3
    Intervention: Drug: AMG 386 30 mg/kg, Capecitabine and Lapatinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
65
December 2014
November 2014   (final data collection date for primary outcome measure)

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)
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   France,   Belgium
 
NCT00807859
20062042
Not Provided
Amgen
Amgen
Not Provided
Study Director: MD Amgen
Amgen
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP