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

NCT01234519 | Terminated Phase 1 DMC

• 2 other identifiers: AEZS-108-046EProst # 20091095
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

Urothelial Carcinoma

Keywords

ureter cancer; renal pelvis cancer; bladder cancer; urethra

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

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

  Day 1 of each 21-day cycle

Secondary Outcomes (5)

• Objective tumor response

  Within 5 days of cycle 4, then every 3 cycles

• Progression-free survival (PFS)

  last cycle

• Pharmacokinetics (PK)

  cycle 1

• Overall survival

  last cycle

• Circulating tumor cell (CTC) levels

  last cycle

Study Arms (5)

Phase 1 - Cohort 1

EXPERIMENTAL

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.

Drug: AEZS-108

Phase 1 - Cohort 2

EXPERIMENTAL

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

Drug: AEZS-108 at MTD

Phase 1 - Cohort 3

EXPERIMENTAL

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

Drug: AEZS-108

Phase 1 - Cohort 4

EXPERIMENTAL

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

Drug: AEZS-108

Phase 2

EXPERIMENTAL

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

Drug: AEZS-108

Interventions

AEZS-108 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

Also known as: ZEN-008, AN-152, D-81858

Phase 1 - Cohort 1; Phase 1 - Cohort 3; Phase 1 - Cohort 4; Phase 2

AEZS-108 at MTD DRUG

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

Also known as: ZEN-008, AN-152, D-81858

Phase 1 - Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AEterna Zentaris: lead
• University of Miami: collaborator
• Miami VA Healthcare System: collaborator
• University of Miami Sylvester Comprehensive Cancer Center: collaborator

Study Sites (2)

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Univerity of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Ureteral Neoplasms; Urinary Bladder Neoplasms

Interventions

LHRH, lysine(6)-doxorubicin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Ureteral Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases

Study Officials

• Gustavo Fernandez, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 2, 2010
• First Posted: November 4, 2010
• Study Start: November 1, 2010
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: March 15, 2018

Record last verified: 2013-03

Locations

US (2)