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

This study has been terminated.
(Poor recruitment)
Sponsor:
Information provided by (Responsible Party):
AEterna Zentaris
ClinicalTrials.gov Identifier:
NCT01698281
First received: September 21, 2012
Last updated: January 14, 2014
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Zoptarelin doxorubicin
Drug: paclitaxel
Drug: nab-paclitaxel
Drug: eribulin
Drug: pegylated liposomal doxorubicin
Drug: vinorelbine
Drug: gemcitabine
Drug: capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Trial of AEZS-108 in Chemotherapy Refractory Triple Negative, LHRH-positive Metastatic Breast Cancer.

Resource links provided by NLM:


Further study details as provided by AEterna Zentaris:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy of AEZS-108 [ Time Frame: Up to two years ] [ Designated as safety issue: Yes ]
  • Overall response of AEZS-108 [ Time Frame: Up to two years ] [ Designated as safety issue: Yes ]
  • Clinical benefit of AEZS-108 [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
  • Duration of response of AEZS-108 [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
  • Overall survival of AEZS-108 [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
  • Toxicity of AEZS-108 [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: December 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AEZS-108
AEZS-108 (267 mg/m2, 2-hour IV infusion every Day 1 of a 21-day (3-week) cycle
Drug: Zoptarelin doxorubicin
Active Comparator: Standard single agent cytotoxic chemotherapy
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).
Drug: paclitaxel Drug: nab-paclitaxel Drug: eribulin Drug: pegylated liposomal doxorubicin Drug: vinorelbine Drug: gemcitabine Drug: capecitabine

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01698281

Locations
United States, Florida
University of Miami
Miami, Florida, United States, 33136
Germany
Universitäts-Frauenklinik
Göttingen, Germany
Klinik für Frauenheilkunde und Geburtshilfe
Regensburg, Germany
Sponsors and Collaborators
AEterna Zentaris
Investigators
Principal Investigator: Alberto J. Montero, MD University of Miami
  More Information

No publications provided

Responsible Party: AEterna Zentaris
ClinicalTrials.gov Identifier: NCT01698281     History of Changes
Other Study ID Numbers: AEZS-108-049
Study First Received: September 21, 2012
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Capecitabine
Liposomal doxorubicin
Doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014