Back to resultsAMG 172 First in Human Study in Patients With Kidney Cancer
Primary Purpose
Renal Cell Adenocarcinoma, Clear Cell Renal Carcinoma, Clear Cell Renal Cell Carcinoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AMG 172
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Adenocarcinoma focused on measuring Amgen, Phase 1, First in Human, Relapsed / Refractory Renal Cell Carcinoma (RCC), Kidney Cancer, Clinical Trial, Antibody drug conjugate (ADC), Open-label, Oncology
Eligibility Criteria
Inclusion Criteria:
- 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)
- Other inclusion criteria may apply
Exclusion Criteria:
- 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
- Other exclusion criteria may apply
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose exploration
Dose expansion
Arm Description
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.
Dose and dosing frequency selected from Part 1 dose exploration.
Outcomes
Primary Outcome Measures
Clinically significant or ≥ Grade 3 CTCAE changes in safety laboratory tests, physical examinations, ECGs, or vital signs
PK parameters including but not limited to, maximum observed concentration (Cmax), area under the concentration-time curve (AUC) and half life (t1/2)
Objective response rate for subjects treated at MTD based on RECIST 1.1
The MTD for at least one of two dosing schedules: every two weeks or every three weeks
Secondary Outcome Measures
Development of human anti-human antibody against AMG 172
Objective response rate for subjects not treated at MTD based on RECIST 1.1
Clinical benefit as measured by duration of response per RECIST 1.1
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01497821
Brief Title
AMG 172 First in Human Study in Patients With Kidney Cancer
Official Title
A Phase 1 First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 172 in Subjects With Relapsed / Refractory Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
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.
Detailed Description
This First in- human study of AMG 172 will be conducted in two parts: Part 1 (dose exploration) and Part 2 (dose expansion). Part 1 of the study is aimed at evaluating the safety, tolerability and PK of AMG 172 given every two weeks and every three weeks in subjects with relapsed / refractory cc RCC, and Part 2 is aimed at evaluating safety, tolerability, PK and response rate in subjects treated at the MTD established in Part 1 for either every two week or every three week dosing. Up to 48 subjects may be enrolled in Part 1, and up to 30 subjects may be enrolled in Part 2. The dose of AMG 172 utilized in Part 2 will be dependent upon data obtained in Part 1 of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Adenocarcinoma, Clear Cell Renal Carcinoma, Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma
Keywords
Amgen, Phase 1, First in Human, Relapsed / Refractory Renal Cell Carcinoma (RCC), Kidney Cancer, Clinical Trial, Antibody drug conjugate (ADC), Open-label, Oncology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose exploration
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose expansion
Arm Type
Experimental
Arm Description
Dose and dosing frequency selected from Part 1 dose exploration.
Intervention Type
Drug
Intervention Name(s)
AMG 172
Intervention Description
AMG 172 is an antibody drug conjugate
Primary Outcome Measure Information:
Title
Clinically significant or ≥ Grade 3 CTCAE changes in safety laboratory tests, physical examinations, ECGs, or vital signs
Time Frame
28 days after the last subject enrolled of each cohort in Part 1 and every 10 subjects enrolled in Part 2 (if available)
Title
PK parameters including but not limited to, maximum observed concentration (Cmax), area under the concentration-time curve (AUC) and half life (t1/2)
Time Frame
12 time points up to 8 weeks
Title
Objective response rate for subjects treated at MTD based on RECIST 1.1
Time Frame
3 years
Title
The MTD for at least one of two dosing schedules: every two weeks or every three weeks
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Development of human anti-human antibody against AMG 172
Time Frame
1 year
Title
Objective response rate for subjects not treated at MTD based on RECIST 1.1
Time Frame
3 years
Title
Clinical benefit as measured by duration of response per RECIST 1.1
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
Other inclusion criteria may apply
Exclusion Criteria:
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
Other exclusion criteria may apply
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
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Research Site
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Research Site
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Research Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
12. IPD Sharing Statement
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
AMG 172 First in Human Study in Patients With Kidney Cancer
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