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Phase 2 Trial of AEZS-108 in Chemotherapy Refractory in Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT01698281
Recruitment Status : Terminated (Poor recruitment)
First Posted : October 2, 2012
Last Update Posted : February 21, 2018
Sponsor:
Information provided by (Responsible Party):
AEterna Zentaris

September 21, 2012
October 2, 2012
February 21, 2018
December 2012
August 2014   (Final data collection date for primary outcome measure)
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 compared to standard single agent cytotoxic chemotherapy (SSCC) as measured by the median time of progression-free survival. [ Time Frame: Up to two years ]
Complete list of historical versions of study NCT01698281 on ClinicalTrials.gov Archive Site
  • 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.
  • Efficacy of AEZS-108 [ Time Frame: Up to two years ]
  • Overall response of AEZS-108 [ Time Frame: Up to two years ]
  • Clinical benefit of AEZS-108 [ Time Frame: up to 2 years ]
  • Duration of response of AEZS-108 [ Time Frame: up to 2 years ]
  • Overall survival of AEZS-108 [ Time Frame: up to 2 years ]
  • Toxicity of AEZS-108 [ Time Frame: up to 2 years ]
Not Provided
Not Provided
 
Phase 2 Trial of AEZS-108 in Chemotherapy Refractory in Triple Negative Breast Cancer
A Randomized Phase 2 Trial of AEZS-108 in Chemotherapy Refractory Triple Negative, LHRH-positive Metastatic Breast Cancer.
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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Breast Cancer
  • Drug: AEZS-108

    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 doxorubicin
  • Drug: SCCC

    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
  • Drug: Dexamethasone
    Recommended prophylactic anti-emetic for AEZS-108: 8 mg dexamethasone.
  • 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
    Interventions:
    • Drug: AEZS-108
    • Drug: 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).

    Intervention: Drug: SCCC
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
7
74
October 2014
August 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Women ≥ 18 years of age
  2. Histologically documented breast cancer (either primary or metastatic site) that is (i) ER-negative (0), (ii) PR-negative (0), 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 of 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.

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/100 mL)
    • 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. Prior exposure to anthracyclines or anthracenediones for the treatment of metastatic breast cancer including liposomal doxorubicin (Doxil), doxorubicin, daunorubicin, or mitoxantrone
  8. Prior adjuvant anthracyclines with a cumulative anthracycline dose ≥ 300 mg/m2
  9. Ongoing therapeutic anticoagulation
  10. 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
  11. 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).
Sexes Eligible for Study: Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Germany,   United States
 
 
NCT01698281
AEZS-108-049
No
Not Provided
Not Provided
AEterna Zentaris
AEterna Zentaris
Not Provided
Principal Investigator: Alberto J. Montero, MD University of Miami
AEterna Zentaris
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP