AMG 172 First in Human Study in Patients With Kidney Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01497821
First received: December 16, 2011
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

This is the first-in-human (Phase I) study of AMG 172, an antibody drug conjugate (ADC), in patients 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 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.


Condition Intervention Phase
Renal Cell Adenocarcinoma
Clear Cell Renal Carcinoma
Clear Cell Renal Cell Carcinoma
Renal Cell Carcinoma
Drug: AMG 172
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Objective response rate for subjects treated at MTD based on RECIST 1.1 [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Development of human anti-human antibody against AMG 172 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Objective response rate for subjects not treated at MTD based on RECIST 1.1 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Clinical benefit as measured by duration of response per RECIST 1.1 [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose exploration
Pre-specified nominal doses are proposed in the dose exploration. 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 selected from Part 1 dose exploration.
Drug: AMG 172
AMG 172 is an antibody drug conjugate

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 in subjects with in subjects with relapsed / refractory cc RCC, and Part 2 is aimed at evaluating safety, tolerability, PK and response rate. Up to 40 subjects may be enrolled in Part 1, and up to 20 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01497821

Contacts
Contact: Amgen Call Center 866-572-6436

Locations
United States, Arizona
Research Site Recruiting
Scottsdale, Arizona, United States, 85258
United States, Missouri
Research Site Recruiting
St Louis, Missouri, United States, 63110
France
Research Site Recruiting
Villejuif, France, 94805
Germany
Research Site Recruiting
Heidelberg, Germany, 69120
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01497821     History of Changes
Other Study ID Numbers: 20090515
Study First Received: December 16, 2011
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration
France: Institutional Ethical Committee
Germany: Ethics Commission

Keywords provided by Amgen:
Amgen
Phase 1
First in Human
Relapsed / Refractory Renal Cell Carcinoma (RCC)
Kidney Cancer
Clinical Trial
Antibody drug conjugate (ADC)
Open-label
Oncology

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on August 21, 2014