Zoptarelin Doxorubicin (AEZS 108) as Second Line Therapy for Endometrial Cancer (ZoptEC)
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| ClinicalTrials.gov Identifier: NCT01767155 |
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Recruitment Status :
Completed
First Posted : January 14, 2013
Results First Posted : July 31, 2018
Last Update Posted : July 31, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Endometrial Cancer | Drug: AEZS-108 / zoptarelin doxorubicin Drug: doxorubicin | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 511 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Randomized Controlled Study Comparing AEZS-108 With Doxorubicin as Second Line Therapy for Locally Advanced, Recurrent or Metastatic Endometrial Cancer. |
| Actual Study Start Date : | April 2013 |
| Actual Primary Completion Date : | January 30, 2017 |
| Actual Study Completion Date : | January 30, 2017 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: AEZS-108 / zoptarelin doxorubicin
267 mg/m^2 by 2-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles up to 9 cycles
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Drug: AEZS-108 / zoptarelin doxorubicin
267 mg/m^2 by 2-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles for a maximum of 9 cycles
Other Name: AEZS-108 |
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Active Comparator: doxorubicin/ standard chemotherapy
60 mg/m^2 by intravenous bolus injection or 1-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles
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Drug: doxorubicin
60 mg/m^2 by intravenous bolus injection or 1-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles |
- Compare the Overall Survival (OS) of Patients Treated With AEZS-108 to the OS of Patients Treated With Doxorubicin. [ Time Frame: From randomization to death from any cause. During ongoing treatment: response evaluation every 3 cycles. For patients gone of treatment: re-assessment every 12 weeks. ]
Overall survival was defined as the elapsed time from randomization to death from any cause. For surviving patients, follow-up was to be censored at the date of last contact.
The final analysis, which was event-based, was conducted after approximately 384 randomized patients had died.
A log-rank test with an overall two sided Type I Error rate of 0.05 after taking the interim analyses into account was used to compare OS between the two treatment arms via a SAS (Statistical Analysis System) LIFETEST procedure. Kaplan Meier estimates were used to calculate median OS and the 95% confidence interval (CI) of the median OS. The proportion of patients alive at 6 and 12 months (from randomization date) and the 95% CIs for these estimated proportions were calculated.
- Compare Efficacy Based on Objective Response Rate (ORR). [ Time Frame: 3 years ]
The ORR was defined as the sum of the Complete Response (CR) and Partial Response (PR).
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) was to have a reduction in the short axis to <10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
All responses were confirmed at least 4 weeks after the initial response was observed. Tumor assessments occurred every 3 cycles (± 7 days) during ongoing treatment then every 3 months (± 7 days) thereafter while the patient was on study. The last assessment occurred either when progression was confirmed or when approximately 384 randomized patients had died.
- Compare Efficacy Based on Progression-free Survival (PFS). [ Time Frame: During ongoing treatment: response evaluation every 3 cycles. For patients gone of treatment: re-assessment every 12 weeks. ]
Progression-free survival (PFS): days between randomization and the date of documented progression or death for any cause that occurred up to the end of the study. For patients whose progression status could not be determined, their PFS data was censored for the last adequate progression assessment date that the patient was confirmed to have no progression.
Response and progression were to be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (uni-dimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes were to be used.
During ongoing treatment, patients were to be re-evaluated for response every 3 cycles (i.e. every 9 weeks).
A subsequent scan was obtained no earlier than 4 weeks following the initial documentation of an objective status of either complete response (CR) or partial response (PR).
- Compare Efficacy Based on Clinical Benefit Rate (CBR). [ Time Frame: 3 years ]
Clinical benefit was defined as having stable disease (SD) or better lasting for at least 9 weeks. The CBR was analyzed using the same methods for the ORR analyses. The analysis of CBR (CR+PR+SD) was performed in the ITT (intention-to-treat) population.
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) was to have a reduction in the short axis to <10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
All responses were confirmed at least 4 weeks after the initial response was observed. Tumor assessments occurred every 3 cycles (± 7 days) during ongoing treatment then every 3 months (± 7 days) thereafter while the patient was on study. The last assessment occurred either when progression was confirmed or when approximately 384 randomized patients had died.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Women ≥ 18 years of age
- Histologically confirmed endometrial cancer
- Advanced (FIGO stage III or IV), recurrent or metastatic disease.
- Measurable or non-measurable disease that has progressed since last treatment.
- 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.
- 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:
- ECOG (Eastern Cooperative Oncology Group) performance status > 2.
- Inadequate hematologic, hepatic or renal function
- Red blood cell transfusion within 2 weeks prior to anticipated start of study treatment.
- History of myocardial infarction, acute inflammatory heart disease, unstable angina, or uncontrolled arrhythmia within the past 6 months.
- 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).
- Concomitant use of prohibited therapy (specified in protocol)
- 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.
- Previous anthracycline-based chemotherapy (daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone and valrubicin), in any formulation.
- Anticipated ongoing concomitant anticancer therapy during the study.
- History of serious co-morbidity or uncontrolled illness that would preclude study therapy, such as active tuberculosis or any other active infection.
- Brain metastasis, leptomeningeal disease.
- Pregnant or lactating female or female of child-bearing potential not employing adequate contraception.
- Subjects with known hypersensitivity to peptide drugs, including LHRH agonists.
- Receipt of 2 or more prior cytotoxic chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer.
- Prior treatment with AEZS-108.
- Use of LHRH agonist or antagonist treatment within 6 months prior to randomization.
- Malignancy within last 5 years except non-melanoma skin cancer.
- Any concomitant disease or condition which would interfere with the subjects' proper completion of the protocol assignment.
- Concomitant or recent treatment with other investigational drug (within 4 weeks or 5 elimination half life times prior to anticipated start of study treatment).
- Lack of ability or willingness to give informed consent.
- Anticipated non-availability for study visits/procedures.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01767155
Show 123 study locations
| Principal Investigator: | David S Miller, MD | University of Texas Southwestern Medical Center, Dallas, USA | |
| Principal Investigator: | Hani Gabra, MD | Imperial College London Hammersmith Campus, London, UK |
Documents provided by AEterna Zentaris:
| Responsible Party: | AEterna Zentaris |
| ClinicalTrials.gov Identifier: | NCT01767155 |
| Other Study ID Numbers: |
AEZS-108-050 |
| First Posted: | January 14, 2013 Key Record Dates |
| Results First Posted: | July 31, 2018 |
| Last Update Posted: | July 31, 2018 |
| Last Verified: | January 2018 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Endometrial Neoplasms Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Neoplasms Uterine Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications |
Urogenital Diseases Genital Diseases Doxorubicin Liposomal doxorubicin Antibiotics, Antineoplastic Antineoplastic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |