Brief Title
A Phase I/II Trial of AEZS-108 in Urothelial Cancer Patients Who Failed Platinum-chemotherapy
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
Brief Summary
The purpose of this study is to determine the appropriate dose of AEZS-108 to treat patients with a tumor of the urinary system.
Detailed Description
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximum tolerated dose (MTD)
Secondary Outcome
Objective tumor response
Condition
Urothelial Carcinoma
Intervention
AEZS-108
Study Arms / Comparison Groups
Phase 1 - Cohort 1
Description: Determination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort). Patients will be enrolled in cohorts of 3 at a specified AEZS-108 dose beginning with 160mg/m^2. Enrollment will be suspended until all members of a cohort have been observed for dose limiting toxicities (DLT) for a period of 3 weeks (1 cycle of AEZS-108) from initial treatment with AEZS-108. Dose escalation will proceed within each cohort according to a specific scheme where DLT is defined.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
12
Start Date
November 2010
Completion Date
November 2014
Primary Completion Date
November 2014
Eligibility Criteria
Inclusion Criteria: - Histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma - Expression of LHRH receptors confirmed by immunohistochemistry on archival cancer tissue - Measurable disease on radiological studies - Patients with Locally advanced unresectable or metastatic urothelial carcinoma - Documented progression on at least one prior chemotherapy regimen which must have incorporated platinum based therapy - Left ventricular ejection fraction (EF) > 50% - Eastern cooperative oncology group (ECOG) status of 0, 1 or 2 - Adequate bone marrow, renal and hepatic function Exclusion Criteria: - Prior treatment with or allergy to any components of AEZS-108 - Active second malignancies other than non-melanoma skin cancers - Ongoing use of an LHRH agonist (or antagonist) - Presence of an active infection or fever > 38.5 C, parenchymal brain metastases or uncontrolled intercurrent illness - Prior exposure to anthracyclines or anthracenediones including doxorubicin, daunorubicin, and mitoxantrone - Patients who received radiotherapy within 4 weeks of entry - Major surgery within the last 4 weeks and minor surgery in last 7 days
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Gustavo Fernandez, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01234519
Organization ID
AEZS-108-046
Secondary IDs
EProst # 20091095
Responsible Party
Sponsor
Study Sponsor
AEterna Zentaris
Collaborators
University of Miami
Study Sponsor
Gustavo Fernandez, MD, Principal Investigator, University of Miami
Verification Date
March 2013