A Phase 1 Study of the Safety and Pharmacokinetics of AGS-16M18 in Subjects With Advanced Renal Cell Cancer

Phase 1

Terminated

• Conditions: Carcinoma, Renal Cell; Kidney Neoplasms; Kidney Diseases
• Interventions: Biological: AGS-16M18

• Registration Number: NCT00816686
• Lead Sponsor: Astellas Pharma Inc

Brief Summary

This is a first in human study of AGS-16M18 given every week to subjects with advanced renal cell cancer. AGS-16M18 will be administered as a 60 minute IV infusion on consecutive days until the disease worsens.

Detailed Description

Subjects will be enrolled sequentially into 5 planned dose cohorts according to a standard, dose escalation study design. A disease assessment will be performed at study week 5 (+/- 3 days) by the investigator. The assessment will be based both on changes in clinical symptoms, and radiographic images. Subjects without evidence of disease progression may receive AGS-16M18 extended therapy at the dose and schedule of their assigned cohort until disease progression or intolerability of AGS-16M18. Disease assessments will be performed every 8 weeks during the extended period. A safety follow-up visit will occur 4 weeks after the last infusion of AGS-16M18.

Study Timeline

• Study Start: 2008-10
• Study First Submitted: 2009-01-01
• Study First Submitted QC: 2009-01-02
• Study First Posted: 2009-01-05
• Primary Completion: 2010-04
• Study Completion: 2010-04
• Status Verified: 2010-05
• Last Update Submitted: 2013-02-26
• Last Update Posted: 2013-02-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Histologic or cytologic diagnosis (recent or remote) of metastatic renal cell carcinoma (including papillary, clear cell, and excluding transitional cell types) that is not amendable to cure by surgery or other means, and must have failed at least one prior systemic therapy, including but not limited to treatment with sunitinib, temsirolimus or sorafenib
• Evaluable/Measureable disease according to Response Criteria for Solid tumors
• Eastern Cooperative Group performance status of 0-1
• Therapeutic anti-coagulation (PT, and/or INR, PTT) permitted, if clinically stable and >/= 3 months from initiation

Exclusion Criteria

• Past or present documented central nervous system (CNS) tumor or CNS metastasis
• Use of investigational drug (including marketed drugs not approved for this indication) within 4 weeks prior to screening or 5 half-lives of the prior investigational drug (whichever is longer)
• History of thromboembolic events and bleeding disorders </= 3 months (e.g., DVT or PE)
• Major Surgery (that requires general anesthesia) within 4 weeks of study enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1. AGS-16M18 Dose 1	AGS-16M18	-
2. AGS-16M18 Dose 2	AGS-16M18	-
3. AGS-16M18 Dose 3	AGS-16M18	-
4. AGS-16M18 Dose 4	AGS-16M18	-
5. AGS-16M18 Dose 5	AGS-16M18	-

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events	Throughout the treatment
Assessment of PK variables	Weeks 0 - 5, week 8, weekly during extension period, 2 and 3 months after last dose

Secondary Outcome Measures

Name	Time	Method
Incidence of anti-AGS-16M18 antibody formation	Week 0, week 1, week 4, week 8, every 8 weeks during extension period, 2 and 3 months after last dose
Changes in tumor status	Week 5, week 8, every 8 weeks during extension period