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

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.

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