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

This study is currently recruiting participants.
Verified January 2014 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00858377
First received: February 26, 2009
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Advanced Malignancy
Advanced Solid Tumors
Cancer
Solid Tumors
Tumors
Drug: Arm 1- Dose Escalation
Drug: Arm 1- Dose Expansion
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in levels of p-Histone H3 from baseline (part 1 - dose escalation only) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Response rate in each taxane-resistant tumor type assessed per RECIST guidelines (part 2 - dose expansion only) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in tumor volume from baseline measured by volumetric CT or MRI [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Tumor response measured by CT or MRI and assessed per RECIST guidelines [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Change from baseline in maximum standardized uptake value (SUVmax) using 18FLT-PET/CT (part 2 - dose expansion only) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 92
Study Start Date: April 2009
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00858377

Contacts
Contact: Amgen Call Center 866-572-6436

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

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00858377     History of Changes
Other Study ID Numbers: 20080016
Study First Received: February 26, 2009
Last Updated: January 30, 2014
Health Authority: United States: Food and Drug Administration
Australia: Ministry of Health

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:
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014