Not provided
Not provided
Not provided
Not provided
Not provided
Poor recruitment
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a therapeutic exploratory Phase 2 study evaluating AEZS-108 compared to standard single agent cytotoxic chemotherapy (SSCC) as measured by the median time of progression-free survival (PFS) in patients with chemotherapy refractory triple negative (ER/PR/HER2-negative) LHRH-R positive metastatic breast cancer.
The study will be conducted as an open-label randomized two-arm multicenter Phase II study. Patients will be randomized in a 1:1 ratio into one of the two treatment arms within each stratum: AEZS-108 (267 mg/m2 every 21 calendar days) (Arm A) OR SSCC (Arm B) at discretion of treating oncologist cycled every 21 calendar days.
Stratified randomization will be used with number of prior lines of therapies (1-2 versus >2). Tumor assessment will be repeated every 2 cycles. At the time of disease progression, Arm B patients may be crossed over to AEZS-108 as long as none of the exclusion criteria for study entry apply. Particularly, LVEF ≥50% is required, and patients failing on liposomal doxorubicin cannot be crossed over to AEZS-108.
Analysis of the main study endpoint, PFS, will follow a group sequential design with one interim and one final analysis utilizing the O'Brien-Fleming stopping boundaries procedure. The study will be terminated for futility if the lower bound is crossed and for superiority if the upper bound is crossed. The sponsor may also terminate the study for futility based on other considerations such as safety.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: AEZS-108 | Experimental | Intervention: AEZS-108 (267 mg/m^2, 2-hour IV infusion every Day 1 of a 21-day (3-week) cycle). Recommended prophylactic anti-emetic for AEZS-108: 8 mg dexamethasone |
|
| Arm B: Standard (SCCC) | Active Comparator | commercially available standard single agent cytotoxic chemotherapy (SSCC): - doses below the recommended package insert at the discretion of treating oncologist; - on a 21-day cycle (although weekly administration is allowed; note: pegylated liposomal doxorubicin will be administered on a 28-day cycle). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AEZS-108 | Drug | AEZS-108 (267 mg/m2, 2-hour IV infusion every Day 1 of a 21-day (3-week) cycle. Allowed delay of re-treatment: up to 2 weeks. Dose reduction: to 210 mg/m2 and 160 mg/m2, if dose limiting toxicity. |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of AEZS-108 compared to SSCC as measured by the median time of progression-free survival (PFS). | PFS is defined as the time elapsed from randomization to the date of documented progression or death, whichever comes first. For surviving patients without progression who begin alternative treatment, PFS will be censored at the last date of documented progression-free status prior to starting alternative treatment. Similarly, losses to follow up will be censored at the last date of documented progression-free status. | Up to two years |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of AEZS-108: overall response | Overall response per RECIST 1.1 (i.e. complete response (CR) + partial response (PR). | Up to two years |
| Efficacy of AEZS-108: clinical benefit | Overall clinical benefit = complete response (CR) + partial response (PR) + stable disease (SD) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status > 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)
Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention
Left ventricular ejection fraction (LVEF) < 50 %, determined by echocardiogram or MUGA scan
Compromised organ or marrow function as evidenced by any of the following:
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
Prior exposure to anthracyclines or anthracenediones for the treatment of metastatic breast cancer including liposomal doxorubicin (Doxil), doxorubicin, daunorubicin, or mitoxantrone
Prior adjuvant anthracyclines with a cumulative anthracycline dose ≥ 300 mg/m2
Ongoing therapeutic anticoagulation
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:
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).
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Alberto J. Montero, MD | University of Miami | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami | Miami | Florida | 33136 | United States | ||
| Universitäts-Frauenklinik |
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C080883 | LHRH, lysine(6)-doxorubicin |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| SCCC | Drug | commercially available SSCC (doses below the recommended package insert at the discretion of treating oncologist), on a 21-day cycle (although weekly administration is allowed; note: pegylated liposomal doxorubicin will be administered on a 28-day cycle). Drugs considered acceptable as SSCC: paclitaxel; nab-paclitaxel; eribulin; pegylated liposomal doxorubicin (PLD); vinorelbine; gemcitabine; capecitabine. Related to PLD: Per notification from EMA (dated 22-Nov-2011) "no new patients should be started on treatment with Caelyx until further notice." Accordingly, this drug may be selected as SSCC treatment option only after such written notice is available. |
|
|
| Dexamethasone | Drug | Recommended prophylactic anti-emetic for AEZS-108: 8 mg dexamethasone. |
|
| up to 2 years |
| Efficacy of AEZS-108: duration of response | The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. | up to 2 years |
| Efficacy of AEZS-108: time to progression (TTP) | TTP is defined as the time elapsed from randomization to the earliest date of documented disease progression. For surviving patients without progression of breast cancer who begin alternative treatment, TTP will be censored at the last date of documented progression-free status prior to starting alternative treatment. This is expected to be negligible and, if the actual data suggest otherwise, competing risk methods will be used instead of Kaplan-Meier estimates. Similarly, losses to follow up will be censored at the last date of documented progression free status. | up to 2 years |
| Efficacy of AEZS-108: overall survival | Overall survival (OS) is defined as the elapsed time from start of therapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact. | up to 2 years |
| Toxicity of AEZS-108 in this patient population | All patients will be evaluable for toxicity from the time of their first treatment with the study drug. | up to 2 years |
| Göttingen |
| Germany |
| Klinik für Frauenheilkunde und Geburtshilfe | Regensburg | Germany |
| D017437 |
| Skin and Connective Tissue Diseases |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |