AMG 172 First in Human Study in Patients With Kidney Cancer

NCT ID: NCT01497821

Last Updated: 2016-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2015-01-31

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.

Conditions

Renal Cell Adenocarcinoma; Clear Cell Renal Carcinoma; Clear Cell Renal Cell Carcinoma; Renal Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

AMG 172

Intervention Type: DRUG

AMG 172 is an antibody drug conjugate

Dose expansion

Dose and dosing frequency selected from Part 1 dose exploration.

Group Type: EXPERIMENTAL

AMG 172

Intervention Type: DRUG

AMG 172 is an antibody drug conjugate

Interventions

AMG 172

AMG 172 is an antibody drug conjugate

Intervention Type: DRUG

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:

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)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Research Site

Scottsdale, Arizona, United States

Research Site

St Louis, Missouri, United States

Research Site

Villejuif, , France

Research Site

Heidelberg, , Germany

Countries

United States; France; Germany

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20090515

Identifier Type: -

Identifier Source: org_study_id