A Study to Determine the Maximum Tolerated Dose of ASG-5ME in Subjects With Castration-Resistant Prostate Cancer

NCT01228760 | Completed Phase 1

• 1 other identifier: ASG-5ME-10-1
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this dose escalation study is to determine the Maximum Tolerated Dose (MTD) and the recommended Phase 2 dose of ASG-5ME in subjects with castration-resistant prostate cancer (CRPC).

Conditions

Prostate Neoplasms

Keywords

Castration-Resistant Prostate Cancer; ASG-5ME; Pharmacokinetics of ASG-5ME

Outcome Measures

Primary Outcomes (2)

• Safety assessed by recording of adverse events, laboratory assessments and vital signs

  For 12 weeks during treatment period and up to 4 weeks follow up

• Pharmacokinetics assessment of ASG-5ME blood levels through analysis of blood samples

  Up to day 15 for cycle 1 and cycle 4 and pre-dose for cycles 2 and 3; every 3 weeks during the second 12 weeks of treatment; and if subject continues on study drug, every 12 weeks thereafter

Secondary Outcomes (6)

• Incidence of anti-ASG-5ME antibody formation

  Baseline; up to day 64 during the first 12 weeks; and if subject continues on study drug, every 3 weeks during the second 12 weeks of treatment and every 12 weeks thereafter

• Incidence of tumor response (complete or partial response)

  Baseline and every 12 weeks while on study drug

• Changes in prostate-specific antigen (PSA) levels

  Baseline; up to day 64 during the first 12 weeks; and if the subject continues on study drug, every 3 weeks thereafter

• Changes in bone scans

  Baseline and every 12 weeks while on study drug

• Changes in circulating tumor cells

  Baseline; up to day 64 during the first 12 weeks; and if the subject continues on study drug, every 3 weeks during the second 12 weeks of treatment and every 12 weeks thereafter

Study Arms (12)

Dose level 1

EXPERIMENTAL

Drug: ASG-5ME

Dose level 2

EXPERIMENTAL

Drug: ASG-5ME

Dose level 3

EXPERIMENTAL

Drug: ASG-5ME

Dose level 4

EXPERIMENTAL

Drug: ASG-5ME

Dose level 5

EXPERIMENTAL

Drug: ASG-5ME

Dose level 5A

EXPERIMENTAL

Drug: ASG-5ME

Dose level 6

EXPERIMENTAL

Drug: ASG-5ME

Dose level 7

EXPERIMENTAL

Drug: ASG-5ME

Dose level 8

EXPERIMENTAL

Drug: ASG-5ME

Dose level 9

EXPERIMENTAL

Drug: ASG-5ME

Chemotherapy-naïve subjects

EXPERIMENTAL

Drug: ASG-5ME

Chemotherapy exposed subjects

EXPERIMENTAL

Drug: ASG-5ME

Interventions

ASG-5ME DRUG

IV

Chemotherapy exposed subjects; Chemotherapy-naïve subjects; Dose level 1; Dose level 2; Dose level 3; Dose level 4; Dose level 5; Dose level 5A; Dose level 6; Dose level 7; Dose level 8; Dose level 9

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has histologically-confirmed castration-resistant prostate cancer and meets at least 1 of the following criteria:
• subject's disease has progressed on or after available standard therapy -OR-
• there is no effective standard therapy available for treating the subject's disease -OR-
• subject or his disease is not suitable for standard therapy -OR-
• subject chooses to defer or decline standard therapy (subject is adequately informed of the availability of clinically meaningful therapy and chooses instead to partake in this research using a product with no documented clinical activity)
• Testosterone ≤ 50 ng/dL
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \> 6 months as evaluated and documented by the investigator
• Hematologic function, as follows (no red blood cell (RBC) or platelet transfusions are allowed within 4 weeks of the first dose of ASG-5ME):
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL
• Renal function, as follows: creatinine ≤ 1.5 x upper limit of normal (ULN), or creatinine clearance of \> 60 mL/min if serum creatinine is \> 2.0 mg/dL
• Total bilirubin \< 1. 5 x ULN
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)≤ 1.5 x ULN

You may not qualify if:

• History of central nervous system metastasis, including incompletely treated epidural disease
• History of other primary malignancy (including premalignant myeloid malignancy e.g. myelodysplastic syndrome), unless:
• Curatively resected non-melanomatous skin cancer
• Other malignancy curatively treated with no known active disease present and no treatment administered for the last 3 years
• Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outsubject medication
• The following treatments are not allowed within 4 weeks of enrollment: cytotoxic chemotherapy, radiation therapy or the dietary supplement PC-SPES
• Use of prednisone (or equivalent corticosteroids) \> 20 mg/day are not allowed. Doses \< 20 mg/day are allowed only if they have been at the same dose for \> 4 weeks
• Use of anti-androgen therapy (ie, flutamide, bicalutamide and nilutamide) within 6 weeks of study enrollment; non-responders to second-line anti-androgen therapy do not require the 6 week withdrawal period
• Monoclonal antibody therapy within 3 months of enrollment with the exception of denosumab (prior or concurrent use of denosumab is allowed)
• Peripheral neuropathy of ≥ grade 2 as defined by the CTCAE criteria version 4.0
• Major surgery (that requires general anesthesia) within 4 weeks of study enrollment
• Active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) within 72 hours of screening
• Use of any investigational drug (including marketed drugs not approved for this indication) within 30 days prior to enrollment
• History of thromboembolic events and bleeding disorders ≤ 3 months (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE))
• Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen

Sponsors & Collaborators

• Astellas Pharma Inc: lead
• Seagen Inc.: collaborator

Study Sites (4)

The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21205, United States

Location

The Karmanos Cancer Institute

Detriot, Michigan, 48201, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

University of Wisconsin Madison, Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

ASG-5ME

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Chief Medical Officer

  Agensys, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2010
• First Posted: October 26, 2010
• Study Start: October 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: June 7, 2013

Record last verified: 2013-06

Locations

US (4)