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A Phase 1 First-in-Human Study Evaluating AMG 900 in Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT00858377
Recruitment Status : Completed
First Posted : March 9, 2009
Last Update Posted : May 6, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief 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. 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

Condition or disease Intervention/treatment Phase
Advanced Malignancy Advanced Solid Tumors Cancer Solid Tumors Tumors Drug: Arm 1- Dose Escalation Drug: Arm 1- Dose Expansion Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 10, 2009
Actual Primary Completion Date : December 31, 2014
Actual Study Completion Date : April 3, 2019

Arm Intervention/treatment
Experimental: Arm 1- Dose Expansion
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.
Drug: Arm 1- Dose Expansion
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).

Experimental: Arm 1- Dose Escalation
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).
Drug: Arm 1- Dose Escalation
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).




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Change in levels of p-Histone H3 from baseline (part 1 - dose escalation only) [ Time Frame: 1 year ]
  4. Response rate in each taxane-resistant tumor type assessed per RECIST guidelines (part 2 - dose expansion only) [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Change in tumor volume from baseline measured by volumetric CT or MRI [ Time Frame: 1 year ]
  2. Tumor response measured by CT or MRI and assessed per RECIST guidelines [ Time Frame: 1 year ]
  3. Change from baseline in maximum standardized uptake value (SUVmax) using 18FLT-PET/CT (part 2 - dose expansion only) [ Time Frame: 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00858377


Locations
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United States, Arizona
Research Site
Tucson, Arizona, United States, 85724
United States, California
Research Site
Los Angeles, California, United States, 90095
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21231
United States, Nevada
Research Site
Las Vegas, Nevada, United States, 89148
United States, New Mexico
Research Site
Albuquerque, New Mexico, United States, 87131
Australia, South Australia
Research Site
Kurralta Park, South Australia, Australia, 5037
Australia, Victoria
Research Site
Bentleigh East, Victoria, Australia, 3165
Research Site
Parkville, Victoria, Australia, 3050
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00858377     History of Changes
Other Study ID Numbers: 20080016
First Posted: March 9, 2009    Key Record Dates
Last Update Posted: May 6, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing
Keywords provided by Amgen:
Amgen
Phase 1
First in Human
Advanced Solid Tumors
Clinical Trial
Aurora kinase inhibitor
Open-label
Oncology
Additional relevant MeSH terms:
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Neoplasms
Complement Factor H
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs