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Triple Negative Breast CancerPhase 2NCT02984683

Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer

A Phase 2 study testing SAR566658 (ACT14884) in people with Triple Negative Breast Cancer, run by Sanofi at 13 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Primary Objective: To evaluate the tumor Objective Response Rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) of SAR566658 in participants with anti-carbonic anhydrase 6 (CA6)-positive metastatic triple negative breast cancer (TNBC). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Triple Negative Breast Cancer
What is being tested?
SAR566658 (ACT14884)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
13 sitesin 5 countries
Study dates
23 Mar 2017to 7 Sep 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Measurable Metastatic TNBC.
  • Participants with CA6-positive disease.
  • Participants received at least 1 prior chemotherapy regimen but no more than 3 for advanced/metastatic disease.
  • Prior anticancer therapy must have contained anthracycline (eg, doxorubicin), if not contraindicated, and a taxane (eg, docetaxel, paclitaxel) in an adjuvant/neo-adjuvant or metastatic setting.

Who cannot join

  • Eastern Cooperative Oncology Group (ECOG) performance status >=2.
  • Participant less than 18 years old.
  • Pregnant or breast-feeding women.
  • Participants with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period and for 6 months following discontinuation of study drug.
  • Wash out period of less than 3 weeks or 5 half-lives from previous antitumor chemotherapy, immunotherapy, or any investigational treatment.
  • History of brain metastasis (other than totally resected or previously irradiated and nonprogressive/relapsed), spinal cord compression or carcinomatous meningitis, or new evidence of brain leptomeningeal disease.
Show all 15Show fewer
  • Prior treatment with eribulin as last prior therapy or prior maytansinoid treatments (DM1 or DM4 antibody-drug conjugates [ADCs]).
  • Known intolerance to infused protein products including other monoclonal antibodies and ADCs.
  • Poor bone marrow reserve and/or poor organ function.
  • Symptomatic peripheral neuropathy Grade >=2.
  • Previous history of chronic corneal diseases (even if asymptomatic) or unresolved acute nonrecurrent corneal conditions.
  • Participants wearing contact lenses who are not willing to stop wearing them for the duration of the study.
  • Medical conditions requiring concomitant administration of strong Cytochrome P450 3A4 (CYP3A4) inhibitors, unless it could be discontinued at least 2 weeks before 1st administration of SAR566658.
  • Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid.
  • The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial locations and contacts

13 sites in 5 countries.

13 sites in 5 countries

Spain6 sites
  • Investigational Site Number 7240002

    Barcelona, 08035

  • Investigational Site Number 7240005

    Lleida, 25198

  • Investigational Site Number 7240001

    Madrid, 28034

  • Investigational Site Number 7240006

    Madrid, 28041

  • Investigational Site Number 7240003

    Seville, 41013

  • Investigational Site Number 7240004

    Valencia, 46010

Other trials in Spain

Italy3 sites
  • Investigational Site Number 3800003

    Genova, 16132

  • Investigational Site Number 3800001

    Milan, 20132

  • Investigational Site Number 3800004

    Roma, 00144

Other trials in Italy

Netherlands2 sites
  • Investigational Site Number 5280001

    Maastricht, 6229 HX

  • Investigational Site Number 5280002

    Rotterdam, 3015 GD

Other trials in Netherlands

Belgium1 site
  • Investigational Site Number 0560001

    Leuven, 3000

Other trials in Belgium

Czechia1 site
  • Investigational Site Number 2030002

    Prague, 12808

Other trials in Czechia

About this study

Official title: Open-label Phase 2 Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer

Primary Objective:

To evaluate the tumor Objective Response Rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) of SAR566658 in participants with anti-carbonic anhydrase 6 (CA6)-positive metastatic triple negative breast cancer (TNBC). Part 1: To select the SAR566658 dose based on ORR and safety of 2 dose levels of SAR566658. Part 2: Part 2a: To demonstrate the activity of SAR566658 based on ORR in participants overexpressing CA6 (membrane intensity of 2+, 3+ in greater than or equal to (>=) 30% of tumor cells) treated at the selected dose in an expanded cohort, in addition to the participants treated in Part 1. - Part 2b: To assess the efficacy in participants with metastatic TNBC and mild CA6 expression.

Read more

Secondary Objectives:

To assess:

  • Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS), and Time To Progression (TTP).
  • The impact of ocular primary prophylaxis on the incidence of keratopathies.
  • The potential immunogenicity of SAR566658.
  • To evaluate the global safety profile.
Read the detailed description

The duration of the study for 1 participant included a screening period of up to 21 days prior to first study drug administration, 3-week treatment cycle(s) (until 30 days after last SAR566658 administration), and a follow-up period. Each participant was treated until radiological disease progression, unacceptable toxicity, or participant's refusal of further study treatment.

Being tested
SAR566658 (ACT14884)
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SAR566658 (ACT14884)Drug

    Pharmaceutical form:Solution Route of administration: Intravenous

Study groups in NCT02984683
Study groupRoleWhat they receive
SAR566658 90 mg/m^2ExperimentalParticipants received SAR566658 90 milligram per square meter (mg/m^2) as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Receives: Drug: SAR566658 (ACT14884)
SAR566658 120 mg/m^2ExperimentalParticipants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Receives: Drug: SAR566658 (ACT14884)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings

    Predefined safety criteria was defined as occurrence of following IMP-related treatment-emergent adverse event (TEAE) (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03): Grade greater than or equal to (>=) 3 TEAE from the System Organ Class (SOC) of eye disorders, Grade >=3 peripheral neuropathy (Preferred Term), Grade >=4 TEAE. Per NCI-CTCAE v4.03, Adverse Events (AE) were graded as follows: Grade 1: Mild; asymptomatic/mild symptoms; Grade 2: Moderate; minimal, local or non-invasive intervention indicated; Grade 3: Severe or medically significant; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; Grade 5: Death related to AE.

    Measured: Up to Cycle 2 (each cycle of 21 days)

  2. Percentage of Participants With Objective Response

    Objective Response in participants was defined as the participants with complete response (CR) and partial response (PR) as best response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). As per RECIST 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

Secondary outcomes (7)
  1. Percentage of Participants With Disease Control

    Disease control in participants was defined as the participants with CR, PR and stable disease (SD) with a duration of at least 3 months. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.

    Measured: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

  2. Duration of Response (DOR)

    DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first radiological documentation of tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.

    Measured: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

  3. Progression Free Survival (PFS)

    PFS was defined as the time interval between the date of first study treatment administration and the date of documented tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions.

    Measured: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

  4. Time to Tumor Progression (TTP)

    TTP was defined as the time interval between the date of first study treatment administration and the date of the first radiologically documented tumor progression. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

    Measured: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

  5. Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events (SAE)

    AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during the on-treatment period (the time from the first treatment administration to the last treatment administration +30 days). An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.

    Measured: Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)

  6. Number of Participants With Keratopathies (Corneal Toxicity)

    Keratopathy is an eye disorder that involves a blister-like swelling of the cornea (the clear layer in front of the iris and pupil). All participants received ocular primary prophylaxis in each eye in order to prevent the occurrence of keratopathies at the time of each infusion (vasoconstrictor, ophthalmic topical steroid, and cold mask on eyes) and steroid eye drops for an additional 2 days following SAR566658 administration.

    Measured: Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)

  7. Number of Participants With Positive Anti-SAR566658 Antibodies Response

    Measured: Up to 3 treatment cycles, each cycle 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2016 (estimated)
  2. Study start23 Mar 2017
  3. Primary completion7 Sep 2018
  4. Study completion7 Sep 2018

Why it stopped: Study discontinued considering the limited clinical benefit combined with a higher than expected rate of known non-serious ophthalmological event.

Resources

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
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02984683
Sponsor's protocol ID
ACT14884
Other IDs
2016-001962-27, U1111-1182-7044, 2016
Status last verified
Aug 2021
First submitted
4 Dec 2016
Last updated
8 Sep 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SAR566658 (ACT14884) in people with Triple Negative Breast Cancer, run by Sanofi at 13 sites in 5 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 4 inclusion and 15 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 8 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Spain, Italy, Netherlands, Belgium, Czechia. 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?

Yes. Results are posted in the registry (first posted 8 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings (time frame: Up to Cycle 2 (each cycle of 21 days)). The study lists 2 primary outcomes in all. 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 8 Sep 2021.

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