NCT01331941

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P50-P75 for phase_1

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 24, 2011

Completed
15 days until next milestone

First Posted

Study publicly available on registry

April 8, 2011

Completed
5 months until next milestone

Study Start

First participant enrolled

September 19, 2011

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 26, 2013

Completed
Last Updated

November 6, 2017

Status Verified

November 1, 2017

Enrollment Period

1.4 years

First QC Date

March 24, 2011

Last Update Submit

November 1, 2017

Conditions

Advanced Solid TumorsKidney DiseaseRenal Impairment

Keywords

AMG 386PharmacokineticRenal Impairment

Outcome Measures

Primary Outcomes (5)

  • Area under the serum concentration-time curve (AUC)

    Week 1-5.

  • Maximum observed concentration (Cmax)

    Week 1-5.

  • Time to maximum concentration (tmax)

    Week 1-5.

  • Minimum observed concentration (Cmin)

    Week 1-5.

  • Clearance (CL) of AMG 386 calculated as dose divided by AUC on week 5.

    Week 1-5

Secondary Outcomes (5)

  • Adverse events as a measure of safety

    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.

  • Changes in vital signs as a measure of safety

    Weekly at each visit AMG 386 is administered up to and including the last study visit 30 days after the last AMG 386 administration.

  • Changes in clinical laboratory tests as a measure of safety

    Weekly from week 1-9 then every 4 weeks thereafter including the last study visit 30 days after the last AMG 386 administration.

  • Anti-AMG 386 antibody formation

    Week 1, week 5, week 9 and every 16 weeks thereafter including the last study visit 30 days after the last AMG 386 administration.

  • Tumor objective response measured by CT or MRI (without Gadolinium contrast agents) and assessed by RECIST 1.1 criteria.

    Week 5 and every 8 weeks thereafter until the subject's end of participation in the study.

Study Arms (4)

Group 1

EXPERIMENTAL

Cancer subjects with normal renal function.

Drug: AMG 386 + PaclitaxelDrug: AMG 386

Group 3

EXPERIMENTAL

Cancer subjects with moderate renal impairment.

Drug: AMG 386 + PaclitaxelDrug: AMG 386

Group 4

EXPERIMENTAL

Cancer subjects with severe renal impairment.

Drug: AMG 386

Group 2

EXPERIMENTAL

Cancer subjects with mild renal impairment.

Drug: AMG 386 + PaclitaxelDrug: AMG 386

Interventions

AMG 386 + PaclitaxelDRUG

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.

Group 1Group 2Group 3
AMG 386DRUG

15 mg/kg IV (in the vein) weekly beginning week 1 day 1 until progression, unacceptable toxicity, or withdrawal of consent.

Group 1Group 2Group 3Group 4

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Research Site

Atlanta, Georgia, 30332, United States

Location

Research Site

Chicago, Illinois, 60637, United States

Location

Research Site

Lebanon, New Hampshire, 03756, United States

Location

Research Site

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

  • 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.

    PMID: 28074547BACKGROUND

Related Links

MeSH Terms

Conditions

Kidney DiseasesRenal Insufficiency

Interventions

trebananibPaclitaxel

Condition Hierarchy (Ancestors)

Urologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 24, 2011

First Posted

April 8, 2011

Study Start

September 19, 2011

Primary Completion

February 26, 2013

Last Updated

November 6, 2017

Record last verified: 2017-11

Locations

US(4)