Randomised controlled study comparing AEZS-108 with doxorubicin as second line therapy for locally advanced, recurrent or metastatic endometrial cancer
- Conditions
- cancer of the inner lining of the uterusendometriumcancer10013364
- Registration Number
- NL-OMON40258
- Lead Sponsor
- Aeterna Zentaris
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 14
1. Woman * 18 years of age
2. Histologically confirmed endometrial adenocarcinoma of any subtype
a) Endometrioid carcinoma
i. variant with squamous differentiations
ii. Villoglandular variant
iii. Secretory variant
iv. Ciliated cell variant
b) Mucinous adenocarcinoma
c) Serous adenocarcinoma
d) Clear cell adenocarcinoma
e) Mixed cell adenocarcinoma
f) Squamous cell carcinoma
g) Transitional cell carcinoma
h) Small cell carcinoma
i) Undifferentiated carcinoma;3. Advanced (FIGO stage III or IV), recurrent or metastatic disease.;4. 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 regiment with platinum and taxane (either as adjuvant or as first line treatment) and who have progressed.;6. Availability of fresh or archival FFPE tumor specimens for analysis of LHRH receptor expression.
1. Eastern Cooperative Oncology Group (ECOG) performance status > 2
2. Inadequate hematologic, hepatic or renal function
- thromobocyte count: < 100 x 109/L;
- absolute neutrophil count (ANC): < 1.5 x 109/L;
- hemoglobin: < 5.6 mmol/L (< 9 g/dL);
- ASAT, ALAT, AP: > 2.5 times upper limit of normal range (ULN) (> 5x ULN if clearly related to liver metastases)
- creatinine, bilirubin: > 1.5x ULN
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 or ECHO.
6. Concomitant use of prohibited therapy (as specified in Section 6.3.2).
7. Chemo-, immune- or hormonetherapy 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. Women of childbearing potential must agree to employ adequate contraception until 6 months after the last dose of study drug, defined as
- complete abstinence (Note: acceptable only as *true abstinence*, i.e. when this is
in line with the preferred and usual lifestyle of the subject. Periodic abstinence, (e.g.,
calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception).;
- any intrauterine device (IUD) with published data showing that the lowest expected failure rate is < 1 % per year; or
- any other methods with published data showing that the lowest expected failure rate is less than 1 % per year.
13. Subjects with known hypersensitivity to peptide drugs, including
LHRH agonists.
Lack of suitability for the trial:
22. Malignancies arising from the uterine Cervix.
23. Uterine sarcomas or mixed epithelial and mesenchymal tumors including carcinosarcoma, adenosarcoma, or carcinofibroma.
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).
Administrative reasons:
20. Lack of availability for willingness to give informed consent.
21. Anticipated non-availability for study visits/procedures.<
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy variable will be overall survival (OS)<br /><br><br /><br>The primary analysis of the primary efficacy variable will be based on the ITT<br /><br>population. The final OS analysis, which is event-based, will be conducted<br /><br>after approximately 384 randomized patients have died. In the primary analysis,<br /><br>a log-rank test with an overall two-sided Type I error rate of 0.05 after<br /><br>taking the interim analyses into account will be used to compare OS between the<br /><br>two treatment arms via a SAS lifetest procedure. Kaplan-Meier estimates will be<br /><br>used to calculate median OS and the 95% confidence interval of the median OS.<br /><br>The proportion of patients alive at six and 12 months (from randomization date)<br /><br>and the 95% confidence intervals for these estimated proportions, if<br /><br>appropriate, will be presented.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Approximately 384 events of deaths will be required to achieve 80 % power to<br /><br>detect a treatment difference at the two-sided 0.05 significance level. It is<br /><br>expected that approximately 500 patients will be enrolled during an estimated<br /><br>24-month recruitment period and will then be followed for 12 months to observe<br /><br>a total of approximately 384 death events. In the sample size calculation, it<br /><br>is assumed that the median OS is 12 months for AEZS-108 and 9 months for<br /><br>doxorubicin. The sample size calculation has taken two planned interim looks<br /><br>into account, the first being a futility analysis only.<br /><br></p><br>