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

Phase 2TerminatedNCT01234519

AEterna Zentaris12 enrolled

Overview

The purpose of this study is to determine the appropriate dose of AEZS-108 to treat patients with a tumor of the urinary system.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Urothelial Carcinoma

Interventions

AEZS-108DRUG

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

AEZS-108 at MTDDRUG

2-hour IV infusion, Day 1 of 21-day cycles , until toxicity or progression, up to 6 cycles

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

University of Miami Miller School of Medicine

Miami, Florida, United States

Univerity of Pennsylvania

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

Maximum tolerated dose (MTD)

Toxicity per Common Terminology Criteria for Adverse Events (CTCAE).

Time frame: Day 1 of each 21-day cycle

Secondary Outcomes

Objective tumor response

Response evaluation criteria in solid tumors (RECIST) criteria.

Time frame: Within 5 days of cycle 4, then every 3 cycles

Progression-free survival (PFS)

Time elapsed from the start of treatment to the date of documented progression or death, whichever comes first.

Time frame: last cycle

Pharmacokinetics (PK)

To evaluate PK parameters of a single dose AEZS-108 and explore whether the PK parameters are associated with cardiac effects as measured by electrocardiography.

Time frame: cycle 1

Overall survival

Time elapsed from the start of treatment until death.

Time frame: last cycle

Circulating tumor cell (CTC) levels

To quantify tumor cells and attempt to correlate their presence and response to the outcomes of this study.

Time frame: last cycle

Data from ClinicalTrials.gov

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