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

NCT ID: NCT01234519

Last Updated: 2018-03-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2014-11-30

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.

Conditions

Urothelial Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 - Cohort 1

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.

Group Type: EXPERIMENTAL

AEZS-108

Intervention Type: DRUG

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

Phase 1 - Cohort 2

Determination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).

Group Type: EXPERIMENTAL

AEZS-108 at MTD

Intervention Type: DRUG

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

Phase 1 - Cohort 3

Determination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).

Group Type: EXPERIMENTAL

AEZS-108

Intervention Type: DRUG

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

Phase 1 - Cohort 4

Determination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).

Group Type: EXPERIMENTAL

AEZS-108

Intervention Type: DRUG

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

Phase 2

AEZS-108 at MTD to determine efficacy in up to 40 patients.

Group Type: EXPERIMENTAL

AEZS-108

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

AEZS-108 at MTD

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

Intervention Type: DRUG

Other Intervention Names

ZEN-008; AN-152; D-81858; ZEN-008; AN-152; D-81858

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: collaborator

Miami VA Healthcare System

FED

Sponsor Role: collaborator

University of Miami Sylvester Comprehensive Cancer Center

OTHER

Sponsor Role: collaborator

AEterna Zentaris

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gustavo Fernandez, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami Miller School of Medicine

Miami, Florida, United States

Univerity of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

EProst # 20091095

Identifier Type: OTHER

Identifier Source: secondary_id

AEZS-108-046

Identifier Type: -

Identifier Source: org_study_id