Studie is gesloten per 29 juni 2015

Randomized controlled study comparing AEZS-108 with doxorubicin as second line therapy for locally advanced, recurrent or metastatic endometrial cancer


AEZS-108 is een nieuw geneesmiddel, bestaand uit een combinatie van een LHRH-agonist met doxorubicine (DOX). Endometriumcarcinomen zijn vrijwel zonder uitzondering positief voor LH-RH receptoren, zodat met dit hybride molecuul tumorcellen specifiek getarget worden. Na progressie op 1e lijns chemotherapie zijn er voor endometriumcarcinoompatienten nauwelijks goede behandelingen beschikbaar.


Randomisering (1:1)naar één van twee armen:
A: AEZS-108 267 mg/m2 i.v. in 2 h q. 21 dagen, max. 9. Uitstel max 2 weken, dosisreductie tot 210 mg/m2 acceptabel.
B: Doxorubicine 60 mg/m2 i.v. bolus injectie q. 21 dagen, max 8. Uitstel max 2 weken, dosisreductie tot 50% acceptabel.
Responsevaluatie elke 3 kuren (in beide armen)

Eindpunten van de studie:
Vergelijken overall survival (OS) van patienten behandeld met AEZS-108 vs doxorubicine. Secundaire eindpunten zijn progression-free survival (PFS), overall response rate (ORR), en clinical benefit rate (CBR), met geplande subgroup analyses gerelateerd aan  tumor LHRH receptor expressie. Voorts veiligheid en QoL.

Inclusie criteria
1. Women ≥ 18 years of age
2. Histologically confirmed endometrial cancer (hoeft niet van recidief)
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 who have progressed after prior first line treatment with platinum/taxane based chemotherapy for advanced, recurrent or metastatic endometrial cancer.
6. Availability of fresh or archival FFPE tumor specimens for analysis of LHRH receptor expression.

Exclusie criteria
Safety concerns:
1. ECOG performance status > 2.
2. Inadequate hematologic, hepatic or renal function - thrombocyte count: < 75x109/L; - absolute neutrophil count (ANC): < 1.5x109/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, unstable angina, or uncontrolled arrhythmia within the past 6 months.
5. Impaired cardiac function defined as left ventricular ejection fraction (LVEF) < 50 % as measured by MUGA or ECHO.
6. Planned concomitant use of potentially cardiotoxic medication (as specified in Appendix 4).
7. Chemo-, immune-, hormone-, or radiotherapy (including pre- or post-operative brachytherapy) within 4 weeks prior to randomization.
8. Previous anthracycline-based chemotherapy (see Appendix 4 for drug names).
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 defined as - complete abstinence; - 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.
Lack of suitability for the trial:
13. Receipt of 2 or more prior chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer.
14. Prior treatment with AEZS-108.
15. Use of LHRH agonist or antagonist treatment within 6 months prior to randomization (see Appendix 5 for examples for drug names).
16. Malignancy within last 5 years except non-melanoma skin cancer.
17. Any concomitant disease or condition which would interfere with the subjects’ proper completion of the protocol assignment.
18. Concomitant or recent treatment with other investigational drug (within 8 weeks or 5 elimination half life times prior to anticipated start of study treatment).
Administrative reasons:
19. Lack of ability or willingness to give informed consent.
20. Anticipated non-availability for study visits/procedures.

Deelnemende centra in NL: AMC, UMC Groningen, MUMC Maastricht

Contact persoon:
A.M. Westermann, medisch oncoloog AMC, Amsterdam