Clinical trial NCT01234519: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Urothelial Carcinoma
Keywords: ureter cancer
renal pelvis cancer
bladder cancer
urethra
Lead sponsor: AEterna Zentaris
Sponsor class: INDUSTRY
Collaborators: name: University of Miami
name: Miami VA Healthcare System
name: University of Miami Sylvester Comprehensive Cancer Center
First posted: 2010-11-04
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1 : conventional 3+3 design. Phase 2: Simon's two-stage design will be utilized. In Stage I, 22 patients will be treated with the dose determined in Phase I. The study will be terminated for futility if no more than 2 patients out of the 22 patients in Stage I are responders. If 3 or more responders are observed, an additional 18 patients will be enrolled. If at least 8 out of the 40 patients are responders, the treatment will be considered worthy of further development.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Day 1 of each 21-day cycle
Secondary outcomes:
measure: Objective tumor response
timeFrame: Within 5 days of cycle 4, then every 3 cycles
measure: Progression-free survival (PFS)
timeFrame: last cycle
measure: Pharmacokinetics (PK)
timeFrame: cycle 1
measure: Overall survival
timeFrame: last cycle
measure: Circulating tumor cell (CTC) levels
timeFrame: last cycle
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Philadelphia
country: United States
facility: Univerity of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Miami
name: Gustavo Fernandez, MD
role: PRINCIPAL_INVESTIGATOR
References: