AMG 172 First in Human Study in Patients With Kidney Cancer

Renal Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01497821
• Other study ID #: 20090515
• Status: Completed
• Phase: Phase 1
• First received: December 16, 2011
• Last updated: March 23, 2016
• Start date: January 2012
• Est. completion date: January 2015

Study information

• Verified date: March 2016
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFrance: Institutional Ethical CommitteeGermany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: January 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Carcinoma
• Clear Cell Renal Cell Carcinoma
• Kidney Neoplasms
• Renal Cell Adenocarcinoma
• Renal Cell Carcinoma

Intervention

Drug:
• AMG 172
AMG 172 is an antibody drug conjugate

Locations

Country	Name	City	State
France	Research Site	Villejuif
Germany	Research Site	Heidelberg
United States	Research Site	Scottsdale	Arizona
United States	Research Site	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Primary	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	No
Primary	Objective response rate for subjects treated at MTD based on RECIST 1.1		3 years	No
Primary	The MTD for at least one of two dosing schedules: every two weeks or every three weeks		3 years	Yes
Secondary	Development of human anti-human antibody against AMG 172		1 year	Yes
Secondary	Objective response rate for subjects not treated at MTD based on RECIST 1.1		3 years	No
Secondary	Clinical benefit as measured by duration of response per RECIST 1.1		3 years	No

External Links

•   AmgenTrials clinical trials website