Advanced MalignancyPhase 1NCT00858377
A Phase 1 First-in-Human Study Evaluating AMG 900 in Advanced Solid Tumors
A Phase 1 study testing Arm 1- Dose Escalation and Arm 1- Dose Expansion in people with Advanced Malignancy and Advanced Solid Tumors, run by Amgen at 8 sites in 2 countries.
Trial summary
This first-in-human study of AMG 900 will be conducted in two parts: dose escalation and dose expansion. The dose escalation part of the study is aimed at evaluating the safety, tolerability and PK of oral AMG 900 in subjects with advanced solid tumors. Up to 50 subjects may be enrolled in dose escalation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignancy, Advanced Solid Tumors, Cancer
- What is being tested?
- Arm 1- Dose Escalation and Arm 1- Dose Expansion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 10 Aug 2009to 3 Apr 2019
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women ≥ 18 years old
- Part 1 Dose Escalation only: advanced solid tumor refractory to standard treatment for which no standard therapy is available or the subject refuses standard therapy
- Part 1 Dose Escalation only: Measurable or evaluable disease per RECIST guidelines
- Part 2 Dose Expansion only: Taxane-resistant tumor (defined as refractory to or progression within 6 months of discontinuing paclitaxel or docetaxel) of prespecified histology
- Part 2 Dose Expansion only: Measurable disease per RECIST guidelines
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
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- Life expectancy of > 3 months, in the opinion of the investigator
- Willing to provide existing and/or future paraffin-embedded tumor samples
- Part 1 Dose Escalation: must have tumor tissue that is accessible for biopsy by fine needle aspiration (FNA) and must consent to undergo biopsies of their tumor (subjects in non-accelerated phase only)
- Ability to take oral medications
- Competent to sign and date an Institutional Review Board approved informed consent form
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Hemoglobin > 9 g/dL
- Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 x upper limit of normal (ULN)
- Serum creatinine < 2.0 mg/dL
- Calculated creatinine clearance ≥ 50 ml/min
- AST < 2.5 x ULN (if liver or bone metastases are present, ≤ 5 x ULN)
- ALT < 2.5 x ULN (if liver or bone metastases are present, ≤ 5 x ULN)
- Alkaline phosphatase < 2.0 x ULN (if liver or bone metastases are present, ≤ 5 x ULN)
- Total bilirubin < 1.5 x ULN
Who cannot join
- Active parenchymal brain metastases. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade < 1; b) no dexamethasone requirement; and c) follow-up MRI shows no new lesions appearing
- Prior bone marrow transplant (autologous or allogeneic)
- History or presence of hematological malignancies
- History of bleeding diathesis
- Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
- Active peptic ulcer disease
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- Gastrointestinal (GI) tract disease causing the inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (eg, Crohn's disease, ulcerative colitis)
- Active infection requiring intravenous (IV) antibiotics within 2 weeks of study enrollment (day 1)
- Known positive test for HIV
- Active or chronic hepatitis B or hepatitis C infection, determined by serologic tests
- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia
- Anti-tumor therapy within 28 days of study day 1; concurrent use of hormone deprivation therapy for hormone-refractory prostate cancer or breast cancer is permitted
- Treatment with immune modulators including, but not limited to, corticosteroids, cyclosporine and tacrolimus within two weeks prior to enrollment
- Therapeutic or palliative radiation therapy within two weeks of study day 1
- Systemic anticoagulation therapy, including warfarin, within 28 days of day 1
- Prior treatment with aurora inhibitors
- Prior participation in an investigational study (drug or device) within 28 days of study day 1
- Major surgery within 28 days of study day 1
- Any co-morbid medical disorder that may increase the risk of toxicity, in the opinion of the investigator or sponsor
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States5 sites
Research Site
Albuquerque, New Mexico, 87131
Research Site
Baltimore, Maryland, 21231
Research Site
Las Vegas, Nevada, 89148
Research Site
Los Angeles, California, 90095
Research Site
Tucson, Arizona, 85724
Australia3 sites
Research Site
Bentleigh East, Victoria, 3165
Research Site
Kurralta Park, South Australia, 5037
Research Site
Parkville, Victoria, 3050
About this study
Official title: A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered AMG 900 in Adult Subjects With Advanced Solid Tumors
This first-in-human study of AMG 900 will be conducted in two parts: dose escalation and dose expansion. The dose escalation part of the study is aimed at evaluating the safety, tolerability and PK of oral AMG 900 in subjects with advanced solid tumors. Up to 50 subjects may be enrolled in dose escalation. The dose expansion part of the study will consist of 42 subjects in three taxane-resistant tumor types. The dose of AMG 900 will be dependent upon data from the dose escalation part of the study
Read the detailed description
that G-CSF must be started at day 5, 1 day after the last day of AMG 900 and be continued until neutrophiles are > 1000 or until day 12, meaning 2 days before the reinduction.
- Conditions
- Advanced Malignancy, Advanced Solid Tumors, Cancer, Solid Tumors, Tumors
- Being tested
- Arm 1- Dose Escalation, Arm 1- Dose Expansion
- Keywords
- Amgen, Phase 1, First in Human, Advanced Solid Tumors, Clinical Trial, Aurora kinase inhibitor, Open-label, Oncology
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm 1- Dose EscalationDrug
AMG 900 is a small molecule inhibitor of aurora kinases A, B and C. AMG 900 will be administered daily for 4 days every 2 weeks (i.e., 4 consecutive days of dosing followed by 10 consecutive days off treatment).
Arm 1- Dose ExpansionDrug
AMG 900 is a small molecule inhibitor of aurora kinases A, B and C. AMG 900 will be administered daily for 4 days every 2 weeks (i.e., 4 consecutive days of dosing followed by 10 consecutive days off treatment).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1- Dose Expansion | Experimental | The dose expansion part of the study will begin after completion of the dose escalation phase and will consist of 3 cohorts of 14 subjects each. One taxane-resistant tumor type will be evaluated in each cohort. Receives: Drug: Arm 1- Dose Expansion |
| Arm 1- Dose Escalation | Experimental | The dose escalation part of the study is aimed at determining the maximum tolerated dose (MTD) of AMG 900 and if necessary, the MTD with prophylactic GCSF support (MTD-G). Receives: Drug: Arm 1- Dose Escalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: subject incidence of adverse events, first-cycle DLTs and clinically significant changes in vital signs, weight, ECGs and clinical laboratory tests
Measured: 1 year
PK profile: AMG 900 PK parameters including, but not limited to, maximum observed concentration (Cmax), minimum observed concentration, area under the plasma concentration-time curve and, if feasible, half-life
Measured: 1 year
Change in levels of p-Histone H3 from baseline (part 1 - dose escalation only)
Measured: 1 year
Response rate in each taxane-resistant tumor type assessed per RECIST guidelines (part 2 - dose expansion only)
Measured: 1 year
Secondary outcomes (3)
Change in tumor volume from baseline measured by volumetric CT or MRI
Measured: 1 year
Tumor response measured by CT or MRI and assessed per RECIST guidelines
Measured: 1 year
Change from baseline in maximum standardized uptake value (SUVmax) using 18FLT-PET/CT (part 2 - dose expansion only)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2009 (estimated)
- Study start10 Aug 2009
- Primary completion31 Dec 2014
- Study completion3 Apr 2019
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 Advanced MalignancyStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 95 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
- NCT00858377
- Sponsor's protocol ID
- 20080016
- Status last verified
- May 2019
- First submitted
- 26 Feb 2009
- Last updated
- 6 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
Carducci M, Shaheen M, Markman B, Hurvitz S, Mahadevan D, Kotasek D, Goodman OB Jr, Rasmussen E, Chow V, Juan G, Friberg GR, Gamelin E, Vogl FD, Desai J. A phase 1, first-in-human study of AMG 900, an orally administered pan-Aurora kinase inhibitor, in adult patients with advanced solid tumors. Invest New Drugs. 2018 Dec;36(6):1060-1071. doi: 10.1007/s10637-018-0625-6. Epub 2018 Jul 7.
PubMed 29980894
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered AMG 900 in Adult Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00858377
- Acronym / sponsor ID
- 20080016
- Conditions
- Advanced Malignancy, Advanced Solid Tumors, Cancer, Solid Tumors, Tumors
- Keywords
- Amgen, Phase 1, First in Human, Advanced Solid Tumors, Clinical Trial, Aurora kinase inhibitor, Open-label, Oncology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 10 Aug 2009 (actual)
- Primary completion
- 31 Dec 2014 (actual)
- Study completion
- 3 Apr 2019 (actual)
- First posted
- 9 Mar 2009 (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 first-in-human study of AMG 900 will be conducted in two parts: dose escalation and dose expansion. The dose escalation part of the study is aimed at evaluating the safety, tolerability and PK of oral AMG 900 in subjects with advanced solid tumors. Up to 50 subjects may be enrolled in dose escalation. The dose expansion part of the study will consist of 42 subjects in three taxane-resistant tumor types. The dose of AMG 900 will be dependent upon data from the dose escalation part of the study
Detailed description
that G-CSF must be started at day 5, 1 day after the last day of AMG 900 and be continued until neutrophiles are > 1000 or until day 12, meaning 2 days before the reinduction.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1- Dose Expansion | Experimental | Drug: Arm 1- Dose ExpansionThe dose expansion part of the study will begin after completion of the dose escalation phase and will consist of 3 cohorts of 14 subjects each. One taxane-resistant tumor type will be evaluated in each cohort. |
| Arm 1- Dose Escalation | Experimental | Drug: Arm 1- Dose EscalationThe dose escalation part of the study is aimed at determining the maximum tolerated dose (MTD) of AMG 900 and if necessary, the MTD with prophylactic GCSF support (MTD-G). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Men or women ≥ 18 years old
- Part 1 Dose Escalation only: advanced solid tumor refractory to standard treatment for which no standard therapy is available or the subject refuses standard therapy
- Part 1 Dose Escalation only: Measurable or evaluable disease per RECIST guidelines
- Part 2 Dose Expansion only: Taxane-resistant tumor (defined as refractory to or progression within 6 months of discontinuing paclitaxel or docetaxel) of prespecified histology
- Part 2 Dose Expansion only: Measurable disease per RECIST guidelines
Key exclusion criteria (19 listed)
- Active parenchymal brain metastases. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade < 1; b) no dexamethasone requirement; and c) follow-up MRI shows no new lesions appearing
- Prior bone marrow transplant (autologous or allogeneic)
- History or presence of hematological malignancies
- History of bleeding diathesis
- Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
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 |
|---|---|---|
| Arm 1- Dose EscalationAMG 900 is a small molecule inhibitor of aurora kinases A, B and C. AMG 900 will be administered daily for 4 days every 2 weeks (i.e., 4 consecutive days of dosing followed by 10 consecutive days off treatment). | Drug | Arm 1- Dose Escalation |
| Arm 1- Dose ExpansionAMG 900 is a small molecule inhibitor of aurora kinases A, B and C. AMG 900 will be administered daily for 4 days every 2 weeks (i.e., 4 consecutive days of dosing followed by 10 consecutive days off treatment). | Drug | Arm 1- Dose Expansion |
Primary outcome
Safety: subject incidence of adverse events, first-cycle DLTs and clinically significant changes in vital signs, weight, ECGs and clinical laboratory tests
Time frame: 1 year
PK profile: AMG 900 PK parameters including, but not limited to, maximum observed concentration (Cmax), minimum observed concentration, area under the plasma concentration-time curve and, if feasible, half-life
Time frame: 1 year
Change in levels of p-Histone H3 from baseline (part 1 - dose escalation only)
Time frame: 1 year
Response rate in each taxane-resistant tumor type assessed per RECIST guidelines (part 2 - dose expansion only)
Time frame: 1 year
3 secondary outcomes
Change in tumor volume from baseline measured by volumetric CT or MRI
Time frame: 1 year
Tumor response measured by CT or MRI and assessed per RECIST guidelines
Time frame: 1 year
Change from baseline in maximum standardized uptake value (SUVmax) using 18FLT-PET/CT (part 2 - dose expansion only)
Time frame: 1 year
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 6 May 2019.
- Derived from this study: PubMed 29980894Carducci M, Shaheen M, Markman B, Hurvitz S, Mahadevan D, Kotasek D, Goodman OB Jr, Rasmussen E, Chow V, Juan G, Friberg GR, Gamelin E, Vogl FD, Desai J. A phase 1, first-in-human study of AMG 900, an orally administered pan-Aurora kinase inhibitor, in adult patients with advanced solid tumors. Invest New Drugs. 2018 Dec;36(6):1060-1071. doi: 10.1007/s10637-018-0625-6. Epub 2018 Jul 7.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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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
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Arm 1- Dose Escalation and Arm 1- Dose Expansion in people with Advanced Malignancy and Advanced Solid Tumors, run by Amgen at 8 sites in 2 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 21 inclusion and 19 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 6 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Australia. 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?
Safety: subject incidence of adverse events, first-cycle DLTs and clinically significant changes in vital signs, weight, ECGs and clinical laboratory tests (time frame: 1 year). The study lists 4 primary outcomes in all. 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 NCT00858377, 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 6 May 2019; AzTrials last refreshed its copy on 29 Oct 2026.