Urothelial Carcinoma
Conditions
Keywords
ureter cancer, renal pelvis cancer, bladder cancer, urethra
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.
Interventions
DRUGAEZS-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
DRUGAEZS-108 at MTD
2-hour IV infusion, Day 1 of 21-day cycles , until toxicity or progression, up to 6 cycles
Sponsors
University of Miami
Miami VA Healthcare System
University of Miami Sylvester Comprehensive Cancer Center
AEterna Zentaris
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | Day 1 of each 21-day cycle | Toxicity per Common Terminology Criteria for Adverse Events (CTCAE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective tumor response | Within 5 days of cycle 4, then every 3 cycles | Response evaluation criteria in solid tumors (RECIST) criteria. |
| Progression-free survival (PFS) | last cycle | Time elapsed from the start of treatment to the date of documented progression or death, whichever comes first. |
| Pharmacokinetics (PK) | cycle 1 | 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. |
| Overall survival | last cycle | Time elapsed from the start of treatment until death. |
| Circulating tumor cell (CTC) levels | last cycle | To quantify tumor cells and attempt to correlate their presence and response to the outcomes of this study. |
Countries
United States
Outcome results
None listed