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

This study has been terminated.
(Poor recruitment)
Sponsor:
Collaborators:
University of Miami
Miami VA Healthcare System
University of Miami Sylvester Comprehensive Cancer Center
Information provided by (Responsible Party):
AEterna Zentaris
ClinicalTrials.gov Identifier:
NCT01234519
First received: November 2, 2010
Last updated: January 14, 2014
Last verified: March 2013
  Purpose

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
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

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 ] [ Designated as safety issue: Yes ]
    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 ] [ 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 ]

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234519

Locations
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
Investigators
Principal Investigator: Gustavo Fernandez, MD University of Miami
  More Information

No publications provided

Responsible Party: AEterna Zentaris
ClinicalTrials.gov Identifier: NCT01234519     History of Changes
Other Study ID Numbers: AEZS-108-046, EProst # 20091095
Study First Received: November 2, 2010
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on July 22, 2014