Zoptarelin Doxorubicin (AEZS 108) as Second Line Therapy for Endometrial Cancer (ZoptEC)

AEterna Zentaris

Status and phase: Completed; Phase 3

Conditions: Endometrial Cancer

Treatments: Drug: doxorubicin; Drug: AEZS-108 / zoptarelin doxorubicin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01767155

AEZS-108-050

Details and patient eligibility

About

Open-label, randomized, active-controlled, two-arm Phase III study to compare the efficacy and safety of AEZS-108 and doxorubicin.

Full description

The study will include about 500 patients with endometrial cancer resistant to platinum/taxane-based chemotherapy.

Enrollment: 511 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Women ≥ 18 years of age
2. Histologically confirmed endometrial cancer
3. Advanced (FIGO stage III or IV), recurrent or metastatic disease.
4. Measurable or non-measurable disease that has progressed since last treatment.
5. 5. Patients with advanced, recurrent or metastatic endometrial cancer who have received one chemotherapeutic regimen with platinum and taxane (either as adjuvant or as first line treatment) and who have progressed.
6. Availability of fresh or archival FFPE (formalin-fixed and paraffin-embedded) tumor specimens for analysis of LHRH (luteinizing hormone releasing hormone) receptor expression.

Exclusion criteria

1. ECOG (Eastern Cooperative Oncology Group) performance status > 2.
2. Inadequate hematologic, hepatic or renal function
3. Red blood cell transfusion within 2 weeks prior to anticipated start of study treatment.
4. History of myocardial infarction, acute inflammatory heart disease, unstable angina, or uncontrolled arrhythmia within the past 6 months.
5. Impaired cardiac function defined as left ventricular ejection fraction (LVEF) < 50 % (or below the study site's lower limit of normal) as measured by MUGA (multigated radionuclide angiography) or ECHO (echocardiography).
6. Concomitant use of prohibited therapy (specified in protocol)
7. Chemo-, immune-, or hormone-therapy within 5 elimination half life times or 4 weeks prior to randomization, whichever is the shorter. Radiotherapy (including pre- or post-operative brachytherapy) within 4 weeks prior to randomization.
8. Previous anthracycline-based chemotherapy (daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone and valrubicin), in any formulation.
9. Anticipated ongoing concomitant anticancer therapy during the study.
10. History of serious co-morbidity or uncontrolled illness that would preclude study therapy, such as active tuberculosis or any other active infection.
11. Brain metastasis, leptomeningeal disease.
12. Pregnant or lactating female or female of child-bearing potential not employing adequate contraception.
13. Subjects with known hypersensitivity to peptide drugs, including LHRH agonists.
14. Receipt of 2 or more prior cytotoxic chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer.
15. Prior treatment with AEZS-108.
16. Use of LHRH agonist or antagonist treatment within 6 months prior to randomization.
17. Malignancy within last 5 years except non-melanoma skin cancer.
18. Any concomitant disease or condition which would interfere with the subjects' proper completion of the protocol assignment.
19. Concomitant or recent treatment with other investigational drug (within 4 weeks or 5 elimination half life times prior to anticipated start of study treatment).
20. Lack of ability or willingness to give informed consent.
21. Anticipated non-availability for study visits/procedures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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511 participants in 2 patient groups

AEZS-108 / zoptarelin doxorubicin

Experimental group

Description:

267 mg/m\^2 by 2-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles up to 9 cycles

Treatment:

Drug: AEZS-108 / zoptarelin doxorubicin

doxorubicin/ standard chemotherapy

Active Comparator group

Description:

60 mg/m\^2 by intravenous bolus injection or 1-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles

Treatment:

Drug: doxorubicin