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Completed

NCT Number: NCT01767155

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

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

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Key information

Conditions

Endometrial Cancer Endometrial Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Neoplasms Neoplasms by Site Urogenital Diseases Urogenital Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Medizinische Universität Innsbruck, Innsbruck, Austria

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

AEZS-108 / zoptarelin doxorubicin

Drug

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 names: AEZS-108

Doxorubicin

Drug

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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).

  3. 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.

Sponsors and collaborators

Lead sponsor

AEterna Zentaris

Industry

Registry information

Official study title

Randomized Controlled Study Comparing AEZS-108 With Doxorubicin as Second Line Therapy for Locally Advanced, Recurrent or Metastatic Endometrial Cancer.

Acronym: ZoptEC

Important dates

Study start
2013
Primary completion
2017
Study completion
2017
First posted
Jan 14, 2013
Registry last updated
Jul 31, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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