Phase 2 Trial of AEZS-108 in Chemotherapy Refractory in Triple Negative Breast Cancer
|ClinicalTrials.gov Identifier: NCT01698281|
Recruitment Status : Terminated (Poor recruitment)
First Posted : October 2, 2012
Last Update Posted : February 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: AEZS-108 Drug: SCCC Drug: Dexamethasone||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase 2 Trial of AEZS-108 in Chemotherapy Refractory Triple Negative, LHRH-positive Metastatic Breast Cancer.|
|Study Start Date :||December 2012|
|Primary Completion Date :||August 2014|
|Study Completion Date :||October 2014|
Experimental: Arm A: AEZS-108
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
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.
Other Name: Zoptarelin doxorubicinDrug: Dexamethasone
Recommended prophylactic anti-emetic for AEZS-108: 8 mg dexamethasone.
Active Comparator: Arm B: Standard (SCCC)
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).
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.
Other Name: Standard single agent cytotoxic chemotherapy
- Efficacy of AEZS-108 compared to SSCC as measured by the median time of progression-free survival (PFS). [ Time Frame: Up to two years ]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.
- Efficacy of AEZS-108: overall response [ Time Frame: Up to two years ]Overall response per RECIST 1.1 (i.e. complete response (CR) + partial response (PR).
- Efficacy of AEZS-108: clinical benefit [ Time Frame: up to 2 years ]Overall clinical benefit = complete response (CR) + partial response (PR) + stable disease (SD)
- Efficacy of AEZS-108: duration of response [ Time Frame: up to 2 years ]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.
- Efficacy of AEZS-108: time to progression (TTP) [ Time Frame: up to 2 years ]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.
- Efficacy of AEZS-108: overall survival [ Time Frame: up to 2 years ]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.
- Toxicity of AEZS-108 in this patient population [ Time Frame: up to 2 years ]All patients will be evaluable for toxicity from the time of their first treatment with the study drug.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01698281
|United States, Florida|
|University of Miami|
|Miami, Florida, United States, 33136|
|Klinik für Frauenheilkunde und Geburtshilfe|
|Principal Investigator:||Alberto J. Montero, MD||University of Miami|