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Urothelial CarcinomaPhase 1/2NCT01234519

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

A Phase 1/2 study testing AEZS-108 and AEZS-108 at MTD in people with Urothelial Carcinoma, run by AEterna Zentaris at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
AEZS-108 and AEZS-108 at MTD
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesUnited States
Study dates
Nov 2010to Nov 2014
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Univerity of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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

The purpose of this study is to determine the appropriate dose of AEZS-108 to treat patients with a tumor of the urinary system.

Read the 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.

Being tested
AEZS-108, AEZS-108 at MTD
Keywords
ureter cancer, renal pelvis cancer, bladder cancer, urethra
Medical subject headings
Carcinoma, Transitional Cell, Ureteral Neoplasms, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AEZS-108Drug

    Also called ZEN-008, AN-152, D-81858

    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 MTDDrug

    Also called ZEN-008, AN-152, D-81858

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

Study groups in NCT01234519
Study groupRoleWhat they receive
Phase 1 - Cohort 1ExperimentalDetermination 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.
Receives: Drug: AEZS-108
Phase 1 - Cohort 2ExperimentalDetermination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).
Receives: Drug: AEZS-108 at MTD
Phase 1 - Cohort 3ExperimentalDetermination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).
Receives: Drug: AEZS-108
Phase 1 - Cohort 4ExperimentalDetermination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).
Receives: Drug: AEZS-108
Phase 2ExperimentalAEZS-108 at MTD to determine efficacy in up to 40 patients.
Receives: Drug: AEZS-108

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD)

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

    Measured: Day 1 of each 21-day cycle

Secondary outcomes (5)

  1. Objective tumor response

    Response evaluation criteria in solid tumors (RECIST) criteria.

    Measured: Within 5 days of cycle 4, then every 3 cycles

  2. Progression-free survival (PFS)

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

    Measured: last cycle

  3. 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.

    Measured: cycle 1

  4. Overall survival

    Time elapsed from the start of treatment until death.

    Measured: last cycle

  5. Circulating tumor cell (CTC) levels

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

    Measured: last cycle

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2010 (estimated)
  2. Study startNov 2010
  3. Primary completionNov 2014
  4. Study completionNov 2014

Why it stopped: Poor recruitment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
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)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01234519
Sponsor's protocol ID
AEZS-108-046
Other IDs
EProst # 20091095
Status last verified
Mar 2013
First submitted
2 Nov 2010
Last updated
15 Mar 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AEZS-108 and AEZS-108 at MTD in people with Urothelial Carcinoma, run by AEterna Zentaris at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) (time frame: Day 1 of each 21-day cycle). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01234519.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2018.

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