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A Pharmacokinetic Study of AMG 386 in Cancer Subjects With Normal and Impaired Renal Function

Primary Purpose

Advanced Solid Tumors, Kidney Disease, Renal Impairment

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AMG 386 + Paclitaxel
AMG 386
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumors focused on measuring AMG 386, Pharmacokinetic, Renal Impairment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Men or women ≥ 18 years of age
  • Must have a pathologically documented, and definitively diagnosed, advanced solid tumor that is refractory to standard treatment, or for which no curative therapy is available, or for subjects who refuse standard therapy
  • Evaluable OR measurable disease by RECIST 1.1 criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Life expectancy of > 3 months, in the opinion of and as documented by the investigator
  • Subject or subject's legally acceptable representative has provided informed consent

Exclusion Criteria:

  • Subjects with gastric cancer or any malignancy with purely squamous cell histology
  • Known history of primary central nervous system (CNS) tumors or CNS metastases
  • Myocardial infarction within 1 year before study day 1, unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association > class II, uncontrolled hypertension [diastolic > 90 mmHg; systolic > 150 mmHg in repeated measurements])
  • History of stroke, arterial or venous thrombosis, or pulmonary embolism within 1 year before study day 1
  • Active grade 2 or greater peripheral vascular disease or peripheral edema
  • History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis)
  • Non-healing wound, ulcer (including gastrointestinal) or fracture
  • Known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection
  • Major surgery within 4 weeks before study day 1
  • Absolute neutrophils count (ANC) < 1.0 x 10^9/L; or platelet count < 100 x 10^9/L; or hemoglobin < 9 g/dL; or PTT / aPTT > 1.5 x institutional upper limit of normal (ULN) ); or INR > 1.5
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN (> 5.0 x ULN if liver metastases present)
  • Alkaline phosphatase > 2.5 x ULN (> 5.0 x ULN if attributable to liver or bone metastasis)
  • Total bilirubin > 1.5 x ULN
  • Other investigational procedures during the study
  • Previous anti-cancer therapy or investigational agent within 4 weeks prior to study day 1
  • Anticoagulation therapy within 4 weeks of study day 1 and while on study (except low dose warfarin (≤ 2 mg/kg) for prophylaxis against central venous catheter thrombosis)
  • Men and women of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study and an additional 6 months after the last dose of AMG 386. Highly effective methods of birth control include sexual abstinence (men, women); vasectomy or a condom with spermicide (men) in combination with barrier methods, hormonal birth control or IUD (women).
  • Women who are lactating/breastfeeding.
  • Women with a positive pregnancy test.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 1

Group 3

Group 4

Group 2

Arm Description

Cancer subjects with normal renal function.

Cancer subjects with moderate renal impairment.

Cancer subjects with severe renal impairment.

Cancer subjects with mild renal impairment.

Outcomes

Primary Outcome Measures

Area under the serum concentration-time curve (AUC)
Maximum observed concentration (Cmax)
Time to maximum concentration (tmax)
Minimum observed concentration (Cmin)
Clearance (CL) of AMG 386 calculated as dose divided by AUC on week 5.

Secondary Outcome Measures

Adverse events as a measure of safety
Changes in vital signs as a measure of safety
Changes in clinical laboratory tests as a measure of safety
Anti-AMG 386 antibody formation
Tumor objective response measured by CT or MRI (without Gadolinium contrast agents) and assessed by RECIST 1.1 criteria.

Full Information

First Posted
March 24, 2011
Last Updated
November 1, 2017
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT01331941
Brief Title
A Pharmacokinetic Study of AMG 386 in Cancer Subjects With Normal and Impaired Renal Function
Official Title
An Open-label Pharmacokinetic Study of AMG 386 in Advanced Cancer Subjects With Normal and Impaired Renal Function
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
September 19, 2011 (Actual)
Primary Completion Date
February 26, 2013 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

5. Study Description

Brief Summary
This is a phase 1, open-label pharmacokinetic study where up to 40 subjects with advanced solid tumors (up to 6-10 with normal renal function and up to 18-30 with varying degrees of renal dysfunction) will receive weekly doses of AMG 386 intravenously. The primary objective is to evaluate the pharmacokinetics (PK) of single agent AMG 386 in subjects with various degrees of renal function. Once the AMG 386 PK characterization is complete in the first 5 weeks of the study, all subjects will be allowed to continue to receive AMG 386 weekly only or subjects in group 1, 2 or 3 can opt to receive AMG 386 weekly in combination with paclitaxel until disease progression, unacceptable toxicity or withdrawal of consent.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumors, Kidney Disease, Renal Impairment
Keywords
AMG 386, Pharmacokinetic, Renal Impairment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
Cancer subjects with normal renal function.
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Cancer subjects with moderate renal impairment.
Arm Title
Group 4
Arm Type
Experimental
Arm Description
Cancer subjects with severe renal impairment.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Cancer subjects with mild renal impairment.
Intervention Type
Drug
Intervention Name(s)
AMG 386 + Paclitaxel
Intervention Description
15 mg/kg IV (in the vein) of AMG 386 weekly + 80 mg/m^2 IV (in the vein) 3 weeks on/1 week off, optional beginning week 6 until progression, unacceptable toxicity, or withdrawal of consent.
Intervention Type
Drug
Intervention Name(s)
AMG 386
Intervention Description
15 mg/kg IV (in the vein) weekly beginning week 1 day 1 until progression, unacceptable toxicity, or withdrawal of consent.
Primary Outcome Measure Information:
Title
Area under the serum concentration-time curve (AUC)
Time Frame
Week 1-5.
Title
Maximum observed concentration (Cmax)
Time Frame
Week 1-5.
Title
Time to maximum concentration (tmax)
Time Frame
Week 1-5.
Title
Minimum observed concentration (Cmin)
Time Frame
Week 1-5.
Title
Clearance (CL) of AMG 386 calculated as dose divided by AUC on week 5.
Time Frame
Week 1-5
Secondary Outcome Measure Information:
Title
Adverse events as a measure of safety
Time Frame
Weekly at each visit AMG 386 is administered, on day 30, 31 and 32 when only PK assessments are scheduled up to and including the last study visit 30 days after the last AMG 386 administration.
Title
Changes in vital signs as a measure of safety
Time Frame
Weekly at each visit AMG 386 is administered up to and including the last study visit 30 days after the last AMG 386 administration.
Title
Changes in clinical laboratory tests as a measure of safety
Time Frame
Weekly from week 1-9 then every 4 weeks thereafter including the last study visit 30 days after the last AMG 386 administration.
Title
Anti-AMG 386 antibody formation
Time Frame
Week 1, week 5, week 9 and every 16 weeks thereafter including the last study visit 30 days after the last AMG 386 administration.
Title
Tumor objective response measured by CT or MRI (without Gadolinium contrast agents) and assessed by RECIST 1.1 criteria.
Time Frame
Week 5 and every 8 weeks thereafter until the subject's end of participation in the study.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men or women ≥ 18 years of age Must have a pathologically documented, and definitively diagnosed, advanced solid tumor that is refractory to standard treatment, or for which no curative therapy is available, or for subjects who refuse standard therapy Evaluable OR measurable disease by RECIST 1.1 criteria Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Life expectancy of > 3 months, in the opinion of and as documented by the investigator Subject or subject's legally acceptable representative has provided informed consent Exclusion Criteria: Subjects with gastric cancer or any malignancy with purely squamous cell histology Known history of primary central nervous system (CNS) tumors or CNS metastases Myocardial infarction within 1 year before study day 1, unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association > class II, uncontrolled hypertension [diastolic > 90 mmHg; systolic > 150 mmHg in repeated measurements]) History of stroke, arterial or venous thrombosis, or pulmonary embolism within 1 year before study day 1 Active grade 2 or greater peripheral vascular disease or peripheral edema History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) Non-healing wound, ulcer (including gastrointestinal) or fracture Known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection Major surgery within 4 weeks before study day 1 Absolute neutrophils count (ANC) < 1.0 x 10^9/L; or platelet count < 100 x 10^9/L; or hemoglobin < 9 g/dL; or PTT / aPTT > 1.5 x institutional upper limit of normal (ULN) ); or INR > 1.5 Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN (> 5.0 x ULN if liver metastases present) Alkaline phosphatase > 2.5 x ULN (> 5.0 x ULN if attributable to liver or bone metastasis) Total bilirubin > 1.5 x ULN Other investigational procedures during the study Previous anti-cancer therapy or investigational agent within 4 weeks prior to study day 1 Anticoagulation therapy within 4 weeks of study day 1 and while on study (except low dose warfarin (≤ 2 mg/kg) for prophylaxis against central venous catheter thrombosis) Men and women of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study and an additional 6 months after the last dose of AMG 386. Highly effective methods of birth control include sexual abstinence (men, women); vasectomy or a condom with spermicide (men) in combination with barrier methods, hormonal birth control or IUD (women). Women who are lactating/breastfeeding. Women with a positive pregnancy test.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30332
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Research Site
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28074547
Citation
Wu B, Lewis LD, Harvey RD, Rasmussen E, Gamelin E, Sun YN, Friberg G, Koyner JL, Dowlati A, Maitland ML. A Pharmacokinetic and Safety Study of Trebananib, an Fc-Fusion Peptibody, in Patients With Advanced Solid Tumors and Varying Degrees of Renal Dysfunction. Clin Pharmacol Ther. 2017 Aug;102(2):313-320. doi: 10.1002/cpt.617. Epub 2017 Jun 9.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

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A Pharmacokinetic Study of AMG 386 in Cancer Subjects With Normal and Impaired Renal Function

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