Locally Recurrent and Metastatic Breast CancerPhase 1NCT00322400
Phase1b to Evaluate Safety of AMG706 in Combination With Paclitaxel or Docetaxel for Breast Cancer
A Phase 1 study testing Docetaxel, Paclitaxel and AMG 706 in people with Locally Recurrent and Metastatic Breast Cancer, run by Amgen.
Trial summary
This open-label, dose-finding, multi-center study is designed to determine the safety and the maximum tolerated dose of AMG 706 given once daily in combination with either weekly paclitaxel (Arm A) or once-every-3 week docetaxel (Arm B) in subjects with locally recurrent or metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Locally Recurrent and Metastatic Breast Cancer
- What is being tested?
- Docetaxel, Paclitaxel and AMG 706
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- No sites listed yet
- Study dates
- Mar 2006to Jan 2012
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Female 18 years of age or older.
- Adequate hematologic, renal and hepatic function.
- Competent to comprehend, sign, and date an IRB-approved informed consent form.
- Subjects of childbearing potential and sexually active must provide a negative pregnancy test and use accepted and effective method of contraception.
Who cannot join
- Prior taxane-containing treatment within 6 months prior to enrollment.
- Prior treatment including chemotherapy and/or endocrine therapy discontinued < 21 days prior to enrollment.
- More than one prior systemic chemotherapy for locally recurrent or metastatic breast cancer.
- Current or prior history of central nervous system metastases.
- History of arterial or venous thrombosis within 1 year prior to enrollment.
- History of bleeding diathesis or bleeding within 14 days prior to enrollment.
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- Radiation therapy to a significant portion of bone marrow or prior history of high-dose chemotherapy requiring bone marrow or stem cell support.
- Hypersensitivity to paclitaxel, docetaxel, or drugs using the vehicle cremophor.
- Prior VEGFr targeted therapies within 30 days of enrollment.
- Any anticoagulant therapy within 7 days prior to enrollment, except for warfarin of less than 2mg per day.
- Clinically significant cardiac disease including myocardial infarction or other cardiovascular related event within 1 year before enrollment.
- Uncontrolled hypertension (systolic >150 mmHg; diastolic > 90 mmHg).
- Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive.
- Prior bevacizumab or trastuzumab therapy within 12 weeks of enrollment.
- Non-healing wound, ulcer or fracture.
- Known history of prior episodes of cholecystitis, prior biliary procedure or prior or ongoing biliary disease.
- Unable to take oral medications.
- Not recovered from previous therapies.
- Major surgery within 28 days prior to enrollment.
- Prior malignancy unless treated with curative intent and without evidence of disease for greater than 3 years before enrollment.
- Peripheral neuropathy grade > 1 per CTCAE version 3.0
About this study
Official title: An Open-label, Dose-finding Study to Evaluate the Safety of AMG 706 in Combination With Paclitaxel or Docetaxel as Treatment for Locally Recurrent or Metastatic Breast Cancer
This open-label, dose-finding, multi-center study is designed to determine the safety and the maximum tolerated dose of AMG 706 given once daily in combination with either weekly paclitaxel (Arm A) or once-every-3 week docetaxel (Arm B) in subjects with locally recurrent or metastatic breast cancer. Secondarily, this study will evaluate the pharmacokinetic (PK) profile of AMG 706 in both treatment arms, the PK profile of paclitaxel in Arm A and the PK profile of docetaxel in Arm B. Additionally, this study will assess objective tumor response and duration of response. Exploratory endpoints include the investigation of potential biomarker development and to assess the effects of genetic variation in drug metabolism genes, cancer genes and drug target genes on subject response to AMG 706 in combination with paclitaxel or docetaxel.
- Being tested
- Docetaxel, Paclitaxel, AMG 706
- Keywords
- Clinical trial, AMG 706, Anti-angiogenesis, Locally Recurrent, Metastatic, Breast Cancer, VEGF, Angiogenesis Inhibitor, Oral, Multi-kinase Inhibitor, Anti-tumor, PDGF receptor, Paclitaxel, Docetaxel, Targeted Therapy, Oncology, Amgen, c-Kit
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Subjects assigned to Arm B, cohorts will receive 75 or 100 mg/m2 of docetaxel (based on cohort assignment) on Day 1 repeated every 21 days (1 cycle). AMG 706 will be administered concurrently on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond.
PaclitaxelDrug
Subjects assigned to Arm A will receive 90 mg/m2 of paclitaxel on Days 1, 8 and 15 repeated every 28 days (1 cycle). On Arm A, AMG 706 will be concurrently administered on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond.
AMG 706Drug
Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days.
Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days.
| Study group | Role | What they receive |
|---|---|---|
| B1 | Experimental | AMG 706 50 mg daily + Docetaxel (100 mg/m2 D1 every 21 days) Receives: Drug: Docetaxel; Drug: AMG 706 |
| A4 | Experimental | 75 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8 and D15 every 28 days) Receives: Drug: Paclitaxel; Drug: AMG 706 |
| A1 | Experimental | AMG 706 50 mg daily + Paclitaxel (90 mg/m2 D1, D8, D15 every 28 days) Receives: Drug: Paclitaxel; Drug: AMG 706 |
| B4 | Experimental | 75 mg AMG 706 daily + Docetaxel (100 mg/m2, D1 every 21 days) Receives: Drug: Docetaxel; Drug: AMG 706 |
| B5 | Experimental | MTD of AMG 706 + Docetaxel (75mg/m2 D1 every 21 days) Receives: Drug: Docetaxel; Drug: AMG 706 |
| B3 | Experimental | 100 mg AMG 706 daily + Docetaxel (100 mg/m2 on D1 every 21 days) Receives: Drug: Docetaxel; Drug: AMG 706 |
| B2 | Experimental | AMG 706 125 mg daily + Docetaxel (100 mg/m2 D1 every 21 days) Receives: Drug: Docetaxel; Drug: AMG 706 |
| A2 | Experimental | AMG 706 125 mg daily + paclitaxel 90 mg/m2 D1, D8, D15 every 28 days Receives: Drug: Paclitaxel; Drug: AMG 706 |
| A3 | Experimental | 100 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8, and D15 every 28 days) Receives: Drug: Paclitaxel; Drug: AMG 706 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicities (DLTs)
Measured: Cycle 1 of treatment. For Arm A, 1 cycle = 28 days. For Arm B, 1 cycle = 21 days
Secondary outcomes (6)
Pharmacokinetics of AMG 706 when administered with paclitaxel (Arm A) or docetaxel (Arm B)
Measured: Cycle 1 (Arms A and B) and Cycle 2 Arm B only)
Pharmacokinetics of paclitaxel (Arm A) when administered with AMG 706
Measured: Cycle 1, D1 and D8 for subjects in Arm A only
Pharmacokinetics of docetaxel (Arm B) when administered with AMG 706
Measured: Cycles 1 and 2 for subjects in Arm B only
Incidence of adverse events and clinical laboratory abnormalities not defined as DLTs
Measured: From study entry through 30 days post discontinuation of study treatment
Objective tumor response (complete or partial response) according to modified RECIST
Measured: Subjects in Arm A: every 8 weeks until discontuation. Subjects in Arm B:every 6 weeks until discontinuation.
Duration of response (calculated for those subjects who respond): time from first objective tumor response to objective disease progression or death.
Measured: Subjects in Arm A: every 8 weeks until discontuation. Subjects in Arm B:every 6 weeks until discontinuation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2006 (estimated)
- Study startMar 2006
- Primary completionApr 2009
- Study completionJan 2012
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 Locally Recurrent and Metastatic 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
- 46 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
- NCT00322400
- Sponsor's protocol ID
- 20050200
- Status last verified
- Jul 2013
- First submitted
- 4 May 2006
- Last updated
- 31 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
De Boer RH, Kotasek D, White S, Koczwara B, Mainwaring P, Chan A, Melara R, Ye Y, Adewoye AH, Sikorski R, Kaufman PA. Phase 1b dose-finding study of motesanib with docetaxel or paclitaxel in patients with metastatic breast cancer. Breast Cancer Res Treat. 2012 Aug;135(1):241-52. doi: 10.1007/s10549-012-2135-0. Epub 2012 Jul 29.
PubMed 22872523
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Dose-finding Study to Evaluate the Safety of AMG 706 in Combination With Paclitaxel or Docetaxel as Treatment for Locally Recurrent or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00322400
- Acronym / sponsor ID
- 20050200
- Keywords
- Clinical trial, AMG 706, Anti-angiogenesis, Locally Recurrent, Metastatic, Breast Cancer, VEGF, Angiogenesis Inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Mar 2006
- Primary completion
- Apr 2009 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 5 May 2006 (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.
This open-label, dose-finding, multi-center study is designed to determine the safety and the maximum tolerated dose of AMG 706 given once daily in combination with either weekly paclitaxel (Arm A) or once-every-3 week docetaxel (Arm B) in subjects with locally recurrent or metastatic breast cancer. Secondarily, this study will evaluate the pharmacokinetic (PK) profile of AMG 706 in both treatment arms, the PK profile of paclitaxel in Arm A and the PK profile of docetaxel in Arm B. Additionally, this study will assess objective tumor response and duration of response. Exploratory endpoints include the investigation of potential biomarker development and to assess the effects of genetic variation in drug metabolism genes, cancer genes and drug target genes on subject response to AMG 706 in combination with paclitaxel or docetaxel.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| B1 | Experimental | Drug: Docetaxel, Drug: AMG 706AMG 706 50 mg daily + Docetaxel (100 mg/m2 D1 every 21 days) |
| A4 | Experimental | Drug: Paclitaxel, Drug: AMG 70675 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8 and D15 every 28 days) |
| A1 | Experimental | Drug: Paclitaxel, Drug: AMG 706AMG 706 50 mg daily + Paclitaxel (90 mg/m2 D1, D8, D15 every 28 days) |
| B4 | Experimental | Drug: Docetaxel, Drug: AMG 70675 mg AMG 706 daily + Docetaxel (100 mg/m2, D1 every 21 days) |
| B5 | Experimental | Drug: Docetaxel, Drug: AMG 706MTD of AMG 706 + Docetaxel (75mg/m2 D1 every 21 days) |
| B3 | Experimental | Drug: Docetaxel, Drug: AMG 706100 mg AMG 706 daily + Docetaxel (100 mg/m2 on D1 every 21 days) |
| B2 | Experimental | Drug: Docetaxel, Drug: AMG 706AMG 706 125 mg daily + Docetaxel (100 mg/m2 D1 every 21 days) |
| A2 | Experimental | Drug: Paclitaxel, Drug: AMG 706AMG 706 125 mg daily + paclitaxel 90 mg/m2 D1, D8, D15 every 28 days |
| A3 | Experimental | Drug: Paclitaxel, Drug: AMG 706100 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8, and D15 every 28 days) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Female 18 years of age or older.
- Adequate hematologic, renal and hepatic function.
- Competent to comprehend, sign, and date an IRB-approved informed consent form.
Key exclusion criteria (21 listed)
- Prior taxane-containing treatment within 6 months prior to enrollment.
- Prior treatment including chemotherapy and/or endocrine therapy discontinued < 21 days prior to enrollment.
- More than one prior systemic chemotherapy for locally recurrent or metastatic breast cancer.
- Current or prior history of central nervous system metastases.
- History of arterial or venous thrombosis within 1 year prior to enrollment.
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 |
|---|---|---|
| DocetaxelSubjects assigned to Arm B, cohorts will receive 75 or 100 mg/m2 of docetaxel (based on cohort assignment) on Day 1 repeated every 21 days (1 cycle). AMG 706 will be administered concurrently on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond. | Drug | B1, B2, B3, B4, B5 |
| PaclitaxelSubjects assigned to Arm A will receive 90 mg/m2 of paclitaxel on Days 1, 8 and 15 repeated every 28 days (1 cycle). On Arm A, AMG 706 will be concurrently administered on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond. | Drug | A1, A2, A3, A4 |
| AMG 706Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days. | Drug | A1, A2, A3, A4, B1, B2, B3, B4, B5 |
Primary outcome
Incidence of dose limiting toxicities (DLTs)
Time frame: Cycle 1 of treatment. For Arm A, 1 cycle = 28 days. For Arm B, 1 cycle = 21 days
6 secondary outcomes
Pharmacokinetics of AMG 706 when administered with paclitaxel (Arm A) or docetaxel (Arm B)
Time frame: Cycle 1 (Arms A and B) and Cycle 2 Arm B only)
Pharmacokinetics of paclitaxel (Arm A) when administered with AMG 706
Time frame: Cycle 1, D1 and D8 for subjects in Arm A only
Pharmacokinetics of docetaxel (Arm B) when administered with AMG 706
Time frame: Cycles 1 and 2 for subjects in Arm B only
Incidence of adverse events and clinical laboratory abnormalities not defined as DLTs
Time frame: From study entry through 30 days post discontinuation of study treatment
Objective tumor response (complete or partial response) according to modified RECIST
Time frame: Subjects in Arm A: every 8 weeks until discontuation. Subjects in Arm B:every 6 weeks until discontinuation.
Duration of response (calculated for those subjects who respond): time from first objective tumor response to objective disease progression or death.
Time frame: Subjects in Arm A: every 8 weeks until discontuation. Subjects in Arm B:every 6 weeks until discontinuation.
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 31 Jul 2013.
- Results publication: PubMed 22872523De Boer RH, Kotasek D, White S, Koczwara B, Mainwaring P, Chan A, Melara R, Ye Y, Adewoye AH, Sikorski R, Kaufman PA. Phase 1b dose-finding study of motesanib with docetaxel or paclitaxel in patients with metastatic breast cancer. Breast Cancer Res Treat. 2012 Aug;135(1):241-52. doi: 10.1007/s10549-012-2135-0. Epub 2012 Jul 29.
- 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
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Docetaxel, Paclitaxel and AMG 706 in people with Locally Recurrent and Metastatic Breast Cancer, run by Amgen.
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 6 inclusion and 21 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 31 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
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?
Incidence of dose limiting toxicities (DLTs) (time frame: Cycle 1 of treatment. For Arm A, 1 cycle = 28 days. For Arm B, 1 cycle = 21 days). 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 NCT00322400, 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 31 Jul 2013.