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AMG 172 First in Human Study in Patients With Kidney Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01497821
Recruitment Status : Completed
First Posted : December 23, 2011
Last Update Posted : March 25, 2016
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Renal Cell Adenocarcinoma Clear Cell Renal Carcinoma Clear Cell Renal Cell Carcinoma Renal Cell Carcinoma Drug: AMG 172 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : January 2012
Actual Primary Completion Date : November 2014
Actual Study Completion Date : January 2015

Arm Intervention/treatment
Experimental: Dose exploration
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
AMG 172 is an antibody drug conjugate

Experimental: Dose expansion
Dose and dosing frequency selected from Part 1 dose exploration.
Drug: AMG 172
AMG 172 is an antibody drug conjugate

Primary Outcome Measures :
  1. 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) ]
  2. 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 ]
  3. Objective response rate for subjects treated at MTD based on RECIST 1.1 [ Time Frame: 3 years ]
  4. The MTD for at least one of two dosing schedules: every two weeks or every three weeks [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Development of human anti-human antibody against AMG 172 [ Time Frame: 1 year ]
  2. Objective response rate for subjects not treated at MTD based on RECIST 1.1 [ Time Frame: 3 years ]
  3. Clinical benefit as measured by duration of response per RECIST 1.1 [ Time Frame: 3 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L;
    2. Platelet count ≥ 100 x 10^9/L;
    3. 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:

    1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x ULN;
    2. 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);
    3. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01497821

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United States, Arizona
Research Site
Scottsdale, Arizona, United States, 85258
United States, Missouri
Research Site
St Louis, Missouri, United States, 63110
Research Site
Villejuif, France, 94805
Research Site
Heidelberg, Germany, 69120
Sponsors and Collaborators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen Identifier: NCT01497821    
Other Study ID Numbers: 20090515
First Posted: December 23, 2011    Key Record Dates
Last Update Posted: March 25, 2016
Last Verified: March 2016
Keywords provided by Amgen:
Phase 1
First in Human
Relapsed / Refractory Renal Cell Carcinoma (RCC)
Kidney Cancer
Clinical Trial
Antibody drug conjugate (ADC)
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases