A Phase I/II Trial of AEZS-108 in Urothelial Cancer Patients Who Failed Platinum-chemotherapy
The purpose of this study is to determine the appropriate dose of AEZS-108 to treat patients with a tumor of the urinary system.
Drug: AEZS-108 at MTD
|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 I/II Trial of AEZS-108 in Locally Advanced Unresectable or Metastatic Luteinizing Hormone-releasing Hormone(LHRH) Positive Urothelial Carcinoma Patients Who Failed Platinum Based Chemotherapy|
- Maximum tolerated dose (MTD) [ Time Frame: Day 1 of each 21-day cycle ] [ Designated as safety issue: Yes ]Toxicity per Common Terminology Criteria for Adverse Events (CTCAE)
- Objective tumor response [ Time Frame: Within 5 days of cycle 4, then every 3 cycles ] [ Designated as safety issue: No ]Response evaluation criteria in solid tumors (RECIST) criteria
- Progression-free survival [ Time Frame: last cycle ] [ Designated as safety issue: No ]
- Pharmacokinetics [ Time Frame: cycle 1 ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: last cycle ] [ Designated as safety issue: No ]
- Circulating tumor cell levels [ Time Frame: last cycle ] [ Designated as safety issue: No ]
|Study Start Date:||November 2010|
|Estimated Study Completion Date:||November 2015|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Experimental: Phase 1
Maximum tolerated dose (MTD) determination in 4 sequential cohorts of patients (3-6 patients/cohort)
128, 160, 210 or 267 mg/m2, 2-hour intravenous (IV) infusion, Day 1 of 21-day cycles , until toxicity or progression, up to 6 cycles
Experimental: Phase II
AEZS-108 at MTD to determine efficacy in 40 patients
Drug: AEZS-108 at MTD
2-hour IV infusion, Day 1 of 21-day cycles , until toxicity or progression, up to 6 cycles
AEZS-108 is an investigational drug, combining luteinizing hormone-releasing hormone (LHRH), an hormone and doxorubicin (a drug approved to treat different types of cancer).
Some tumors, such as those found in the urinary system (also called urothelial carcinomas), have LHRH hormone receptors to which the LHRH hormone part of AEZS-108 is attracted.
AEZS-108 is expected to work by accumulating mostly on the surface of cancer cells that have LHRH hormone receptors and by delivering doxorubicin more directly into the cells to kill them. This would allow the use doxorubicin at lower doses and thus would cause less toxicity.
In the first part of the study, the appropriate dose of AEZS-108 will be determined based on its side effects. The best dose will be the highest one without severe side effects.
In the second part of the study, this best dose of AEZS-108 will be given to determine its efficacy to stop the tumor from progressing.
|United States, Florida|
|University of Miami Miller School of Medicine|
|Miami, Florida, United States, 33136|
|United States, Pennsylvania|
|Univerity of Pennsylvania|
|Philadelphie, Pennsylvania, United States, 19104|
|Principal Investigator:||Gustavo Fernandez, MD||University of Miami|