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An Open-label, Single Dose Study of the Mass Balance and Metabolic Disposition of Orally Administered [14C]-Labelled AMG 706 (Motesanib) Followed by Extended Treatment With Motesanib in Patients With Advanced Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Advanced Solid Tumors

Thank you

Trial Information

An Open-label, Single Dose Study of the Mass Balance and Metabolic Disposition of Orally Administered [14C]-Labelled AMG 706 (Motesanib) Followed by Extended Treatment With Motesanib in Patients With Advanced Solid Tumors


Inclusion Criteria:



- Subjects with a pathologically documented and definitively diagnosed advanced solid
tumor(excluding tumors that may significantly interfere with the absorption,
metabolism, or excretion of the test article, such as primary or metastatic liver
tumor with approximately >50% of liver tissue involvement) that is refractory to
standard treatment or for which no curative therapy is available

- Eastern Cooperative Oncology Group performance status of 0-1

- Man or woman (male or female), age > 18 years

- Ability to understand and sign an Independent Ethics Committee (IEC) Approved
informed

- Subjects must also fulfil Haematological, Renal, Hepatic and Coagulation criteria
(not listed)

Exclusion Criteria:

- Acute disease state (e.g. nausea, vomiting, fever, diarrhea) within 7 days of Day 1

- History of documented arterial or venous thrombosis within 1 year of Day 1

- History of bleeding diathesis or bleeding within 14 days of Day 1, or
hypercoagulopathy syndrome

- History of life-threatening ventricular arrhythmia (e.g. sustained ventricular
tachycardia)

- History of pulmonary hemorrhage or gross hemoptysis (1/2 teaspoon of bright red blood
or more) within 6 months of Day 1

- Central nervous system metastases (exception: subjects with treated, asymptomatic
central nervous system metastases, those who have been clinically stable in the
judgment of the investigator and off steroids for at least 30 days before Day 1 are
eligible)

- Subjects with non-small cell lung cancer (NSCLC)

- Subjects with head and neck cancer

- Subjects with ovarian cancer

- Subjects with large central (located adjacent to or within the hilum or mediastinum)
tumor lesions ≥ 3 cm, regardless of histology

- Uncontrolled hypertension: average systolic blood pressure > 150 mm Hg or average
diastolic blood pressure > 90 mm Hg (average blood pressure of the three separate
blood pressure values measured within 10 minutes during screening)

- Systemic chemotherapy within 28 days of Day 1

- Radiotherapy within 28 days of Day 1 or within 14 days of Day 1 for peripheral
lesions

- Experimental or approved antibody therapy within 6 weeks before Day 1

- Concurrent or prior (within 4 weeks prior to Day 1 of 5 half-lives of the medication
which ever is longer) treatment with potent CYP3A inducers, including but not limited
to : phenytoin, carbamazepine, rifampicin, phenobarbital and St John's Wort

- Concurrent or prior (within 2 weeks prior to Day 1 or 5 half-lives of the medication
which ever is longer) treatment with potent CYP3A inhibitors, including but not
limited to: ketoconazole, itraconazole, fluconazole, clarithromycin, erythromycin,
cyclosporine, tacrolimus, nefazodone and/or HIV protease inhibitors

- Concurrent or prior (within 2 weeks prior to Day 1) consumption of grapefruit (i.e.
whole fruit or fruit juice)

- Subjects who as a result of gastrointestinal surgeries (including cholecystectomy) or
a medical condition (e.g. constipation, cholecystitis / cholelithiasis) that will
significantly alter the absorption, metabolism or excretion of motesanib.

- Subjects with irregular bowel habits (more than 3/day or less than 1 every 2 days).

- Subjects who will not refrain from taking herbal/ complementary therapies (which have
the potential to alter the absorption, metabolism, or excretion of the [14C]-AMG 706)
for 7 days before first dosing, and for the duration of the ADME part of the study.

- Concurrent immune modulators such as cyclosporine and tacrolimus

- Any anti-coagulation therapy within 7 days prior to Day 1

- Subjects whose occupation requires exposure to radiation or monitoring for radiation
exposure

- Clinically significant cardiac disease within 12 months of study Day 1, including
myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular
disease, cerebrovascular accident, transient ischemic attack, congestive heart
failure, or ongoing arrhythmias requiring medication

- Major surgery (that which requires general anesthesia) within 28 days or minor
surgery within 14 days of Day 1

- Any kind of disorder that compromises the ability of the subject to give written
informed consent and/or comply with the study procedures

- History of any medical or psychiatric condition or laboratory abnormality that in the
opinion of the investigator may increase the risks associated with study
participation or investigational product administration or may interfere with the
interpretation of the study results

- Known positive test for human immunodeficiency virus infection, hepatitis C virus,
chronic active hepatitis B infection or any co-morbid disease that would increase
risk of toxicity

- Any subject not consenting to use adequate contraceptive precautions (eg, hormonal,
barrier or abstinence) during the course of the study and for 6 months after the last
treatment

- Female subjects who have a positive pregnancy test at screening or on Day-1

- Female subjects who are breastfeeding or plan to breastfeed during the study or
within 6 months after the last administration of the investigational product

- Participation in a therapeutic clinical trial within 30 days of Day1

- Subject is unwilling or unable to comply with the study requirements

- Subject has a known sensitivity to any of the products to be administered over the
course of the study (e.g. known hypersensitivity to study medication motesanib)

- Subjects with a history of gall bladder and bile duct disease

- Subjects with Gilberts syndrome

Type of Study:

Interventional

Study Design:

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

Profile and identification of metabolites of [14C]-AMG 706 in plasma, urine, and faeces

Safety Issue:

No

Principal Investigator

MD

Investigator Role:

Study Director

Investigator Affiliation:

Amgen

Authority:

United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:

20080639

NCT ID:

NCT01386866

Start Date:

May 2009

Completion Date:

December 2010

Related Keywords:

  • Advanced Solid Tumors
  • AMG 706
  • Motesanib
  • Amgen
  • Phase 1
  • Neoplasms

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