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

Urothelial Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01234519
• Other study ID #: AEZS-108-046
• Secondary ID: EProst # 2009109
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: November 2, 2010
• Last updated: March 13, 2018
• Start date: November 2010
• Est. completion date: November 2014

Study information

• Verified date: March 2013
• Source: AEterna Zentaris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

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
• AEZS-108 at MTD
2-hour IV infusion, Day 1 of 21-day cycles , until toxicity or progression, up to 6 cycles

Locations

Country	Name	City	State
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Univerity of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
AEterna Zentaris	Miami VA Healthcare System, University of Miami, University of Miami Sylvester Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)	Toxicity per Common Terminology Criteria for Adverse Events (CTCAE).	Day 1 of each 21-day cycle
Secondary	Objective tumor response	Response evaluation criteria in solid tumors (RECIST) criteria.	Within 5 days of cycle 4, then every 3 cycles
Secondary	Progression-free survival (PFS)	Time elapsed from the start of treatment to the date of documented progression or death, whichever comes first.	last cycle
Secondary	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.	cycle 1
Secondary	Overall survival	Time elapsed from the start of treatment until death.	last cycle
Secondary	Circulating tumor cell (CTC) levels	To quantify tumor cells and attempt to correlate their presence and response to the outcomes of this study.	last cycle