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A Phase I/II Trial of AEZS-108 in Urothelial Cancer Patients Who Failed Platinum-chemotherapy

This study has been terminated.
(Poor recruitment)
University of Miami
Miami VA Healthcare System
University of Miami Sylvester Comprehensive Cancer Center
Information provided by (Responsible Party):
AEterna Zentaris Identifier:
First received: November 2, 2010
Last updated: January 14, 2014
Last verified: March 2013
The purpose of this study is to determine the appropriate dose of AEZS-108 to treat patients with a tumor of the urinary system.

Condition Intervention Phase
Urothelial Carcinoma Drug: AEZS-108 Drug: AEZS-108 at MTD Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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

Resource links provided by NLM:

Further study details as provided by AEterna Zentaris:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: Day 1 of each 21-day cycle ]
    Toxicity per Common Terminology Criteria for Adverse Events (CTCAE)

Secondary Outcome Measures:
  • Objective tumor response [ Time Frame: Within 5 days of cycle 4, then every 3 cycles ]
    Response evaluation criteria in solid tumors (RECIST) criteria

  • Progression-free survival [ Time Frame: last cycle ]
  • Pharmacokinetics [ Time Frame: cycle 1 ]
  • Overall survival [ Time Frame: last cycle ]
  • Circulating tumor cell levels [ Time Frame: last cycle ]

Enrollment: 12
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)
Arms Assigned Interventions
Experimental: Phase 1
Maximum tolerated dose (MTD) determination in 4 sequential cohorts of patients (3-6 patients/cohort)
Drug: AEZS-108
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
Other Names:
  • ZEN-008
  • AN-152
  • D-81858
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
Other Names:
  • ZEN-008
  • AN-152
  • D-81858

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01234519

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
Sponsors and Collaborators
AEterna Zentaris
University of Miami
Miami VA Healthcare System
University of Miami Sylvester Comprehensive Cancer Center
Principal Investigator: Gustavo Fernandez, MD University of Miami
  More Information

Responsible Party: AEterna Zentaris Identifier: NCT01234519     History of Changes
Other Study ID Numbers: AEZS-108-046
EProst # 20091095 ( Other Identifier: Sylvester Comprehensive Cancer Center )
Study First Received: November 2, 2010
Last Updated: January 14, 2014

Keywords provided by AEterna Zentaris:
ureter cancer
renal pelvis cancer
bladder cancer

Additional relevant MeSH terms:
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Prolactin Release-Inhibiting Factors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on August 21, 2017