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

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

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