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

NCT01698281 | Terminated Phase 2

• 1 other identifier: AEZS-108-049
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Efficacy of AEZS-108: overall response

  Up to two years

• Efficacy of AEZS-108: clinical benefit

  up to 2 years

• Efficacy of AEZS-108: duration of response

  up to 2 years

• Efficacy of AEZS-108: time to progression (TTP)

  up to 2 years

• Efficacy of AEZS-108: overall survival

  up to 2 years

Study Arms (2)

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

Drug: AEZS-108; Drug: 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).

Drug: SCCC

Interventions

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.

Also known as: Zoptarelin doxorubicin

Arm A: AEZS-108

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.

Also known as: Standard single agent cytotoxic chemotherapy

Arm B: Standard (SCCC)

Dexamethasone DRUG

Recommended prophylactic anti-emetic for AEZS-108: 8 mg dexamethasone.

Arm A: AEZS-108

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ≥ 18 years of age
• 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).
• Expression of LHRH receptor confirmed by IHC on archival (or current biopsy of breast tumor or metastatic site) breast cancer tissue
• Progressive disease after failure of 1 to 3 prior chemotherapy regimens for recurrent or metastatic (Stage IV) disease (prior adjuvant/neoadjuvant therapy is allowed)
• Measurable disease by RECIST 1.1 criteria; at least one target lesion that has not been previously irradiated.

You may not qualify if:

• 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:
• 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.
• 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

Sponsors & Collaborators

• AEterna Zentaris: lead

Study Sites (3)

University of Miami

Miami, Florida, 33136, United States

Location

Universitäts-Frauenklinik

Göttingen, Germany

Location

Klinik für Frauenheilkunde und Geburtshilfe

Regensburg, Germany

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

LHRH, lysine(6)-doxorubicin; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Alberto J. Montero, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2012
• First Posted: October 2, 2012
• Study Start: December 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: October 1, 2014
• Last Updated: February 22, 2018

Record last verified: 2013-05

Locations

US (1); DE (2)