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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00858377
• Other study ID #: 20080016
• Status: Completed
• Phase: Phase 1
• Start date: August 10, 2009
• Est. completion date: April 3, 2019

Study information

• Verified date: May 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: April 3, 2019
• Est. primary completion date: December 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Malignancy
• Advanced Solid Tumors
• Cancer
• Neoplasms
• Solid Tumors
• Tumors

Intervention

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).
• 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).

Locations

Country	Name	City	State
Australia	Research Site	Bentleigh East	Victoria
Australia	Research Site	Kurralta Park	South Australia
Australia	Research Site	Parkville	Victoria
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Baltimore	Maryland
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Los Angeles	California
United States	Research Site	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: subject incidence of adverse events, first-cycle DLTs and clinically significant changes in vital signs, weight, ECGs and clinical laboratory tests		1 year
Primary	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		1 year
Primary	Change in levels of p-Histone H3 from baseline (part 1 - dose escalation only)		1 year
Primary	Response rate in each taxane-resistant tumor type assessed per RECIST guidelines (part 2 - dose expansion only)		1 year
Secondary	Change in tumor volume from baseline measured by volumetric CT or MRI		1 year
Secondary	Tumor response measured by CT or MRI and assessed per RECIST guidelines		1 year
Secondary	Change from baseline in maximum standardized uptake value (SUVmax) using 18FLT-PET/CT (part 2 - dose expansion only)		1 year

External Links

•   AmgenTrials clinical trials website