Clinical trial NCT00807859: Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Breast Neoplasms
Breast Tumors
Cancer
Locally Recurrent and Metastatic Breast Cancer
Metastases
Metastatic Cancer
Oncology
Solid Tumors
Tumors
Keywords: AMG 386
Paclitaxel
Trastuzumab
Capecitabine
Lapatinib
HER2-positive
metastatic breast cancer
locally recurrent breast cancer
Taxol
Herceptin
Xeloda
Tykerb
anti-angiogenic therapy
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2008-12-12
Enrollment: 65
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
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
timeFrame: 24 months
Secondary outcomes:
measure: To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs
timeFrame: 24 months
measure: 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
timeFrame: 24 months
measure: To estimate the incidence of anti AMG 386 antibody formation
timeFrame: 24 months
measure: 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)
timeFrame: 23 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Boca Raton
country: United States
facility: Research Site
state: Florida
city: Iowa City
country: United States
facility: Research Site
state: Iowa
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Lebanon
country: United States
facility: Research Site
state: New Hampshire
city: Lebanon
country: United States
facility: Research Site
state: New Hampshire
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Great Neck
country: United States
facility: Research Site
state: New York
city: New City
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Nyack
country: United States
facility: Research Site
state: New York
city: Middletown
country: United States
facility: Research Site
state: Ohio
city: Leuven
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Wilrijk
country: Belgium
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Caen Cedex 05
country: France
facility: Research Site
city: La Roche Sur Yon Cedex 9
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Nantes Cedex 2
country: France
facility: Research Site
city: Pierre BÃ©nite Cedex
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.