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

Primary Purpose

Urothelial Carcinoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AEZS-108

AEZS-108 at MTD

About this trial

This is an interventional treatment trial for Urothelial Carcinoma focused on measuring ureter cancer, renal pelvis cancer, bladder cancer, urethra

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Miami Miller School of Medicine
Univerity of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Phase 1 - Cohort 1

Phase 1 - Cohort 2

Phase 1 - Cohort 3

Phase 1 - Cohort 4

Phase 2

Arm Description

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.

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

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

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD)

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

Secondary Outcome Measures

Objective tumor response

Response evaluation criteria in solid tumors (RECIST) criteria.

Progression-free survival (PFS)

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

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.

Overall survival

Time elapsed from the start of treatment until death.

Circulating tumor cell (CTC) levels

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

Full Information

NCT ID

NCT01234519

First Posted

November 2, 2010

Last Updated

March 13, 2018

Sponsor

AEterna Zentaris

Collaborators

University of Miami, Miami VA Healthcare System, University of Miami Sylvester Comprehensive Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT01234519

Brief Title

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

2. Study Status

Record Verification Date

March 2013

Overall Recruitment Status

Terminated

Why Stopped

Poor recruitment

Study Start Date

November 2010 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AEterna Zentaris

Collaborators

University of Miami, Miami VA Healthcare System, University of Miami Sylvester Comprehensive Cancer Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Urothelial Carcinoma

Keywords

ureter cancer, renal pelvis cancer, bladder cancer, urethra

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

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.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1 - Cohort 1

Arm Type

Experimental

Arm Description

Arm Title

Phase 1 - Cohort 2

Arm Type

Experimental

Arm Description

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

Arm Title

Phase 1 - Cohort 3

Arm Type

Experimental

Arm Description

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

Arm Title

Phase 1 - Cohort 4

Arm Type

Experimental

Arm Description

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

Arm Title

Phase 2

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

AEZS-108

Other Intervention Name(s)

ZEN-008, AN-152, D-81858

Intervention Description

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

Intervention Name(s)

AEZS-108 at MTD

Other Intervention Name(s)

ZEN-008, AN-152, D-81858

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD)

Description

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

Time Frame

Day 1 of each 21-day cycle

Secondary Outcome Measure Information:

Title

Objective tumor response

Description

Response evaluation criteria in solid tumors (RECIST) criteria.

Time Frame

Within 5 days of cycle 4, then every 3 cycles

Title

Progression-free survival (PFS)

Description

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

Time Frame

last cycle

Title

Pharmacokinetics (PK)

Description

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

Title

Overall survival

Description

Time elapsed from the start of treatment until death.

Time Frame

last cycle

Title

Circulating tumor cell (CTC) levels

Description

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

Time Frame

last cycle

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gustavo Fernandez, MD

Organizational Affiliation

University of Miami

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Miami Miller School of Medicine

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Univerity of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

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

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