Trial with AEZS-108 in a special type of breast tumor

• Conditions: Histologically confirmed malignancy of breast tissue; estrogen- and progesterone receptor negative, non overexpressing HER2-receptors, LHRH receptor positive tumor status; receptor status determined by immunohistochemistry from primary tumor; MedDRA version: 15.0Level: PTClassification code 10057654Term: Breast cancer femaleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-000134-19-DE
• Lead Sponsor: Aeterna Zentaris GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06-21
• Last Update Posted: 14 September 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 74

Inclusion Criteria

1) Woman = 18 years of age
2) Histologically documented breast cancer (either primary or metastatic site) that is
(i) ER-negative,
(ii) PR-negative, and
(iii) HER2-negative, defined by IHC (immunohistochemistry; IHC 0/1, non-overexpressing) or FISH (fluorescence in situ hybridization; FISH negative) or CISH (chromogen in situ hybridization; CISH negative).
3) Expression LHRH receptor confirmed by IHC on archival (or current biopsy of breast tumor or metastatic site) breast cancer tissue.
4) Progressive disease after failure of 1 to 3 prior chemotherapy regimens for recurrent or metastatic (Stage IV) disease (prior adjuvant/neoadjuvant therapy is allowed).
5) Measurable disease by RECIST 1.1 criteria; at least one target lesion that has not been previously irradiated.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Eastern Cooperative Oncology Group (ECOG) performance status > 2
2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or recent myocardial infarction (within 6 months of enrollment)
3. Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention.
4. Left ventricular ejection fraction (LVEF) < 50%, determined by echocardiogram or MUGA scan
5. Compromised organ or marrow function as evidenced by any of the following:
- thrombocyte count: < 100x109/L;
- absolute neutrophil count (ANC): <1.5x109/L;
- hemoglobin: <6.0 mmol/L (<9 g/100mL);
- AS(A)T, AL(A)T: > 2.5 times upper limit of normal range (ULN)
(>5x ULN if clearly related to liver metastases);
- bilirubin: >1.5 mg/dL;
- creatinine: >1.5 mg/dL or creatinine clearance <40 mL/min.
6. Systemic anticancer therapy or radiotherapy within 21 calendar days of the first dose of study drug*).
* also excluded are patients with anticipated ongoing concomitant anticancer therapy during the study
7. History of allergic reaction to anthracycline or peptide drugs, including LHRH agonists.
8. Prior exposure to anthracyclines or anthracenediones for the treatment of metastatic breast cancer including liposomal doxorubicin (Doxil), doxorubicin, daunorubicin, or mitoxantrone.
9. Prior adjuvant anthracyclines with a cumulative anthracycline dose equivalent to = 300 mg/m2 (e.g. 600 mg/m2 in case of epirubicin)
10. Ongoing therapeutic anticoagulation.
11. Patients who are not surgically sterile or post-menopausal must agree to use for the duration of the study reliable methods of birth control 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
12. Use of LHRH agonist or antagonist treatment within 6 months prior to or during the study
13. Investigational therapy within 30 calendar days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication).
14. Prior treatment with AEZS-108.
Administrative reasons
15. Lack of ability or willingness to give informed consent and comply with the protocol.
16. Anticipated non-availability for study visits/procedures.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of AEZS-108 compared to standard single agent cytotoxic chemotherapy (SSCC) as measured by the median time of progression-free survival (PFS).<br>;Secondary Objective: To evaluate efficacy of AEZS-108 compared to standard single agent cytotoxic chemotherapy as measured by the overall response, clinical benefit, duration of response, time to progression, overall survival.<br>To evaluate toxicity of AEZS-108 in this patient population.;Primary end point(s): progression-free survival (PFS);Timepoint(s) of evaluation of this end point: after 60 events of disease progression (interim analysis after 30 events of disease progression)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Overall response<br>2. Clinical benefit<br>3. Duration of response<br>4. Time to progression<br>5. Overall survival<br>6. Toxicity;Timepoint(s) of evaluation of this end point: after 60 events of disease progression