NCT01497821

Brief Summary

This is the first-in-human (Phase I) study of AMG 172, an antibody drug conjugate (ADC), in subjects with kidney cancer \[Clear Cell Renal Cell Carcinoma (ccRCC)\] who have relapsed or who have refractory disease following at least two prior therapies. The purpose of the study is to evaluate safety and pharmacokinetics (PK) of AMG 172, and also evaluate the objective response rate in patients with ccRCC receiving AMG 172. The study will be conducted in two Parts: Part 1 will explore doses of AMG 172 given every two weeks and every three weeks to determine the safety, tolerability and pharmacokinetics to establish a maximum tolerated dose (MTD), and Part 2 (dose expansion) will examine safety, tolerability, PK and overall response rate in subjects treated at the MTD established in Part 1 for either every two week or every three week dosing.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
37

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2012

Typical duration for phase_1

Geographic Reach
3 countries

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

December 16, 2011

Completed
7 days until next milestone

First Posted

Study publicly available on registry

December 23, 2011

Completed
9 days until next milestone

Study Start

First participant enrolled

January 1, 2012

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2014

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
Last Updated

March 25, 2016

Status Verified

March 1, 2016

Enrollment Period

2.8 years

First QC Date

December 16, 2011

Last Update Submit

March 23, 2016

Conditions

Renal Cell AdenocarcinomaClear Cell Renal CarcinomaClear Cell Renal Cell CarcinomaRenal Cell Carcinoma

Keywords

AmgenPhase 1First in HumanRelapsed / Refractory Renal Cell Carcinoma (RCC)Kidney CancerClinical TrialAntibody drug conjugate (ADC)Open-labelOncology

Outcome Measures

Primary Outcomes (4)

  • Clinically significant or ≥ Grade 3 CTCAE changes in safety laboratory tests, physical examinations, ECGs, or vital signs

    28 days after the last subject enrolled of each cohort in Part 1 and every 10 subjects enrolled in Part 2 (if available)

  • PK parameters including but not limited to, maximum observed concentration (Cmax), area under the concentration-time curve (AUC) and half life (t1/2)

    12 time points up to 8 weeks

  • Objective response rate for subjects treated at MTD based on RECIST 1.1

    3 years

  • The MTD for at least one of two dosing schedules: every two weeks or every three weeks

    3 years

Secondary Outcomes (3)

  • Development of human anti-human antibody against AMG 172

    1 year

  • Objective response rate for subjects not treated at MTD based on RECIST 1.1

    3 years

  • Clinical benefit as measured by duration of response per RECIST 1.1

    3 years

Study Arms (2)

Dose exploration

EXPERIMENTAL

Pre-specified nominal doses are proposed in the dose exploration at two dosing frequencies: every two weeks and every three weeks. Intermediate doses may also be used if required based on the Continuous Reassessment Method (CRM) design.

Drug: AMG 172

Dose expansion

EXPERIMENTAL

Dose and dosing frequency selected from Part 1 dose exploration.

Drug: AMG 172

Interventions

AMG 172DRUG

AMG 172 is an antibody drug conjugate

Dose expansionDose exploration

Eligibility Criteria

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

You may qualify if:

  • Subjects must have a pathologically documented, definitively diagnosed, clear cell RCC that is relapsed/refractory following at least two lines of systemic therapy (one of which must be a tyrosine kinase), or the subject refuses standard therapy
  • Measurable disease per RECIST 1.1 criteria. Subjects with non-measurable, but evaluable disease are also eligible for Part 1 of the study.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
  • Willing to provide tumor samples and / or slides
  • Hematological function, as follows:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L;
  • Platelet count ≥ 100 x 10\^9/L;
  • Hemoglobin \> 9 g/dL
  • Prothrombin time (PT) or partial thromboplastin time (PTT) \< 1.5 x institutional upper limit of normal (IULN)
  • Hepatic function, as follows:
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x ULN;
  • Total bilirubin \< 1.5 x ULN (\< 3.0 x ULN for subjects with documented Gilbert's Disease or for whom the indirect bilirubin level suggests an extrahepatic source of elevation);
  • Alkaline phosphatase \< 2 x ULN (\< 5 x ULN in subjects whom the PI and sponsor agree that clinical data suggest extrahepatic source of elevation)

You may not qualify if:

  • Known primary central nervous system (CNS) tumors or brain metastases
  • 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, or uncontrolled hypertension in the opinion of the investigator
  • Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome
  • A baseline ECG QTcF \> 470 msec
  • Known positive test for human immunodeficiency virus (HIV)
  • Known acute or chronic hepatitis B or hepatitis C infection as determined by serologic tests

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Research Site

Scottsdale, Arizona, 85258, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Villejuif, 94805, France

Location

Research Site

Heidelberg, 69120, Germany

Location

Related Links

MeSH Terms

Conditions

Carcinoma, Renal CellKidney NeoplasmsNeoplasms

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Study Design

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

Study Record Dates

First Submitted

December 16, 2011

First Posted

December 23, 2011

Study Start

January 1, 2012

Primary Completion

November 1, 2014

Study Completion

January 1, 2015

Last Updated

March 25, 2016

Record last verified: 2016-03

Locations

DE(1)FR(1)US(2)