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

Tracking Information
First Submitted Date ICMJE	December 11, 2008
First Posted Date ICMJE	December 12, 2008
Last Update Posted Date	November 2, 2015
Study Start Date ICMJE	March 2009
Actual Primary Completion Date	February 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 11, 2008)	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 ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00807859 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 11, 2008)	To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs [ Time Frame: 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 [ Time Frame: 24 months ]; To estimate the incidence of anti AMG 386 antibody formation [ Time Frame: 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) [ Time Frame: 23 months ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer
Official Title ICMJE	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
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Breast Cancer; Breast Neoplasms; Breast Tumors; Cancer; Locally Recurrent and Metastatic Breast Cancer; Metastases; Metastatic Cancer; Oncology; Solid Tumors; Tumors
Intervention ICMJE	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
Study Arms	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
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 15, 2013)	65
Original Estimated Enrollment ICMJE; (submitted: December 11, 2008)	40
Actual Study Completion Date	October 2015
Actual Primary Completion Date	February 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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)
Sex/Gender	Sexes Eligible for Study: Female
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Belgium, France, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00807859
Other Study ID Numbers ICMJE	20062042
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Amgen
Study Sponsor ICMJE	Amgen
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: MD Amgen
PRS Account	Amgen
Verification Date	October 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP