Breast CancerPhase 2NCT01698281
Phase 2 Trial of AEZS-108 in Chemotherapy Refractory in Triple Negative Breast Cancer
A Phase 2 study testing AEZS-108, SCCC and Dexamethasone in people with Breast Cancer, run by AEterna Zentaris at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- AEZS-108, SCCC and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Dec 2012to Oct 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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
- 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:
- 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
- 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).
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Germany2 sites
Universitäts-Frauenklinik
Göttingen
Klinik für Frauenheilkunde und Geburtshilfe
Regensburg
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Breast Cancer
- Being tested
- AEZS-108, SCCC, Dexamethasone
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AEZS-108Drug
Also called Zoptarelin doxorubicin
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.
SCCCDrug
Also called 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).
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.
DexamethasoneDrug
Recommended prophylactic anti-emetic for AEZS-108: 8 mg dexamethasone.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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). Receives: Drug: SCCC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to two years
Secondary outcomes (6)
Efficacy of AEZS-108: overall response
Overall response per RECIST 1.1 (i.e. complete response (CR) + partial response (PR).
Measured: Up to two years
Efficacy of AEZS-108: clinical benefit
Overall clinical benefit = complete response (CR) + partial response (PR) + stable disease (SD)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2012 (estimated)
- Study startDec 2012
- Primary completionAug 2014
- Study completionOct 2014
Why it stopped: Poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- AEterna Zentaris
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alberto J. Montero, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01698281
- Sponsor's protocol ID
- AEZS-108-049
- Status last verified
- May 2013
- First submitted
- 21 Sep 2012
- Last updated
- 22 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2 Trial of AEZS-108 in Chemotherapy Refractory Triple Negative, LHRH-positive Metastatic Breast Cancer.
- ClinicalTrials.gov ID
- NCT01698281
- Acronym / sponsor ID
- AEZS-108-049
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment
- Enrolment
- 7 participants (actual)
- Lead sponsor
- AEterna ZentarisIndustry (pharma, biotech, devices)
- Study start
- Dec 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 2 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: AEZS-108 | Experimental | Drug: AEZS-108, Drug: DexamethasoneIntervention: 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 | Drug: SCCCcommercially 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (21 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AEZS-108Also: Zoptarelin doxorubicinAEZS-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. | Drug | Arm A: AEZS-108 |
| SCCCAlso: Standard single agent cytotoxic chemotherapycommercially 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. | Drug | Arm B: Standard (SCCC) |
| DexamethasoneRecommended prophylactic anti-emetic for AEZS-108: 8 mg dexamethasone. | Drug | Arm A: AEZS-108 |
Primary outcome
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.
6 secondary outcomes
Efficacy of AEZS-108: overall response
Time frame: Up to two years
Efficacy of AEZS-108: clinical benefit
Time frame: up to 2 years
Efficacy of AEZS-108: duration of response
Time frame: up to 2 years
Efficacy of AEZS-108: time to progression (TTP)
Time frame: up to 2 years
Efficacy of AEZS-108: overall survival
Time frame: up to 2 years
Toxicity of AEZS-108 in this patient population
Time frame: up to 2 years
Results and safety
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alberto J. Montero, MD principal investigator
University of Miami
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AEZS-108, SCCC and Dexamethasone in people with Breast Cancer, run by AEterna Zentaris at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2018.