Breast CancerPhase 1NCT00807859
Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer
A Phase 1 study testing AMG 386 30 mg/kg, Paclitaxel and Trastuzumab, AMG 386 30 mg/kg, Capecitabine and Lapatinib and AMG 386 10 mgkg, Paclitaxel and Trastuzumab in people with Breast Cancer and Breast Neoplasms, run by Amgen at 23 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Breast Neoplasms, Breast Tumors
- What is being tested?
- AMG 386 30 mg/kg, Paclitaxel and Trastuzumab, AMG 386 30 mg/kg, Capecitabine and Lapatinib and AMG 386 10 mgkg, Paclitaxel and Trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 23 sitesin 3 countries
- Study dates
- 9 Mar 2009to 19 Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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)
Trial locations and contacts
23 sites in 3 countries.
23 sites in 3 countries
United States13 sites
Research Site
Albuquerque, New Mexico, 87131
Research Site
Boca Raton, Florida, 33428
Research Site
Boston, Massachusetts, 02111
Research Site
Great Neck, New York, 11021
Research Site
Iowa City, Iowa, 52242
Research Site
Lebanon, New Hampshire, 03756-0001
Research Site
Lebanon, New Hampshire, 03756
Research Site
Middletown, Ohio, 45042
Research Site
Minneapolis, Minnesota, 55407
Research Site
New City, New York, 10956
Research Site
New York, New York, 10032
Research Site
Nyack, New York, 10960
Research Site
Tucson, Arizona, 85724
France7 sites
Research Site
Bordeaux, 33075
Research Site
Caen, 14076
Research Site
La Roche-sur-Yon, 85925
Research Site
Marseille, 13009
Research Site
Nantes, 44202
Research Site
Pierre Bénite Cedex, 69495
Research Site
Toulouse, 31052
Belgium3 sites
Research Site
Leuven, 3000
Research Site
Liège, 4000
Research Site
Wilrijk, 2610
About this study
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
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.
- Conditions
- Breast Cancer, Breast Neoplasms, Breast Tumors, Cancer, Locally Recurrent and Metastatic Breast Cancer, Metastases
- Being tested
- AMG 386 30 mg/kg, Paclitaxel and Trastuzumab, AMG 386 30 mg/kg, Capecitabine and Lapatinib, AMG 386 10 mgkg, Paclitaxel and Trastuzumab, AMG 386 10 mg/kg, Capecitabine and Lapatinib
- Keywords
- AMG 386, Paclitaxel, Trastuzumab, Capecitabine, Lapatinib, HER2-positive, metastatic breast cancer, locally recurrent breast cancer, Taxol, Herceptin, Xeloda, Tykerb, anti-angiogenic therapy
- Medical subject headings
- Breast Neoplasms, Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 386 30 mg/kg, Paclitaxel and TrastuzumabDrug
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 LapatinibDrug
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 TrastuzumabDrug
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 LapatinibDrug
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 group | Role | What they receive |
|---|---|---|
| Cohort A1 | Experimental | Not described Receives: Drug: AMG 386 10 mgkg, Paclitaxel and Trastuzumab |
| Cohort A3 | Experimental | Not described Receives: Drug: AMG 386 30 mg/kg, Paclitaxel and Trastuzumab |
| Cohort B1 | Experimental | Not described Receives: Drug: AMG 386 10 mg/kg, Capecitabine and Lapatinib |
| Cohort B3 | Experimental | Not described Receives: Drug: AMG 386 30 mg/kg, Capecitabine and Lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 months
Secondary outcomes (4)
To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs
Measured: 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
Measured: 24 months
To estimate the incidence of anti AMG 386 antibody formation
Measured: 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)
Measured: 23 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2008 (estimated)
- Study start9 Mar 2009
- Primary completion27 Feb 2014
- Study completion19 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00807859
- Sponsor's protocol ID
- 20062042
- Status last verified
- Nov 2022
- First submitted
- 11 Dec 2008
- Last updated
- 8 Nov 2022
- Results posted
- No
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.
PubMed 30420181
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00807859
- Acronym / sponsor ID
- 20062042
- Conditions
- Breast Cancer, Breast Neoplasms, Breast Tumors, Cancer, Locally Recurrent and Metastatic Breast Cancer, Metastases
- Keywords
- AMG 386, Paclitaxel, Trastuzumab, Capecitabine, Lapatinib, HER2-positive, metastatic breast cancer, locally recurrent breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 9 Mar 2009 (actual)
- Primary completion
- 27 Feb 2014 (actual)
- Study completion
- 19 Oct 2015 (actual)
- First posted
- 12 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort A1 | Experimental | Drug: AMG 386 10 mgkg, Paclitaxel and Trastuzumab |
| Cohort A3 | Experimental | Drug: AMG 386 30 mg/kg, Paclitaxel and Trastuzumab |
| Cohort B1 | Experimental | Drug: AMG 386 10 mg/kg, Capecitabine and Lapatinib |
| Cohort B3 | Experimental | Drug: AMG 386 30 mg/kg, Capecitabine and Lapatinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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)
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 386 30 mg/kg, Paclitaxel and TrastuzumabAMG 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 | Cohort A3 |
| AMG 386 30 mg/kg, Capecitabine and LapatinibAMG 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 | Cohort B3 |
| AMG 386 10 mgkg, Paclitaxel and TrastuzumabAMG 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 | Cohort A1 |
| AMG 386 10 mg/kg, Capecitabine and LapatinibAMG 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 | Drug | Cohort B1 |
Primary outcome
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
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Background: PubMed 30420181Kaufman 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
23 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 386 30 mg/kg, Paclitaxel and Trastuzumab, AMG 386 30 mg/kg, Capecitabine and Lapatinib and AMG 386 10 mgkg, Paclitaxel and Trastuzumab in people with Breast Cancer and Breast Neoplasms, run by Amgen at 23 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00807859, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.