Metastatic Breast CancerPhase 2FRIDANCT02370238
A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer
A Phase 2 study testing paclitaxel and Reparixin in people with Metastatic Breast Cancer, run by Dompé Farmaceutici S.p.A at 77 sites in 7 countries.
Trial summary
The Objectives of this study: The primary objective of the study was to evaluate progression-free survival (PFS) (defined as the number of days between the date of randomization and the date of clinical disease progression (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, as… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- paclitaxel and Reparixin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 194 participants
- Where
- 77 sitesin 7 countries
- Study dates
- 29 Jul 2015to 23 Mar 2020
- 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
- Female aged ≥ 18 years.
- Patients with pathologically documented metastatic triple negative breast cancer (TNBC), eligible for treatment with paclitaxel. Paraffin-embedded tissue must be available from metastatic sites, if reasonably accessible, or from the primary tumor, to confirm the diagnosis of TNBC and for correlative studies (only on metastatic tissue). Fifteen slides can be obtained if the full block is not available to be sent or released.
- TNBC will be defined as breast cancer with <1% ER+ and <1% PgR+ cells, and HER2 immunohistochemistry score of 0 or 1+ and/or in situ hybridization (ISH) with HER2 gene copy number <4 or a ratio of less than 2 between HER2 gene copy number and centromere of chromosome 17. Patients whose metastatic disease is TNBC are eligible even when their primary tumor expressed hormone receptors and/or HER2.
- Patients must be newly diagnosed metastatic or must have relapsed following a prior (neo)adjuvant chemotherapy regimen. If a taxane (i.e., paclitaxel or docetaxel) was administered as part of the (neo)adjuvant regimen, PD must have occurred > 12 months from the end of previous (neo)adjuvant treatment. For non-taxane (neo)adjuvant regimen, PD must have occurred > 6 months from the end of previous (neo)adjuvant treatment
- Patients with at least one baseline measurable lesion according to RECIST criteria version 1.1.
- Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0-1.
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- Life expectancy of at least three months.
- Patients must be able to swallow and retain oral medication (intact tablet).
- Able to undergo all screening assessments outlined in the protocol.
- Adequate organ function (defined by the following parameters):
- Serum creatinine < 140 μmol/L (< 1.6 mg/dL) or creatinine clearance > 60 mL/min.
- Serum hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L.
- Serum bilirubin ≤ 1.5 x upper normal limit (UNL) except patients with Gilbert's syndrome
- Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x UNL but ≤ 5.0 x UNL in case of liver metastases; alkaline phosphatase (ALP) ≤ UNL but i) ≤ 2.5 x UNL in case of liver metastases and ii) ≤ 5 UNL in case of bone metastases; albumin ≥ 2.5 g/dl.
- No history or evidence by CT scan or MRI, of brain metastases or leptomeningeal disease.
- No known hepatitis B virus (not due to immunization), hepatitis C virus, human immunodeficiency virus-I and -II positive status.
- Dated and signed IEC/IRB-approved informed consent.
Who cannot join
- Prior therapy for metastatic TNBC (chemotherapy, hormone therapy or biological therapy), Patients may receive bisphosphonates and other therapies to treat bone metastases, however if used, bone lesions will not be considered as measurable disease.
- Less than four weeks since last radiotherapy (excluding palliative radiotherapy).
- Pregnancy or lactation or unwillingness to use adequate method of birth control.
- Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.
- Active or uncontrolled infection.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function.
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- G>1 pre-existing peripheral neuropathy
- Any other invasive malignancy from which the patient has been disease-free for less than 5 years with the exception of curatively treated basal or squamous cell skin cancer
- Hypersensitivity to:
- paclitaxel
- ibuprofen or to more than one non-steroidal anti-inflammatory drug.
- medications belonging to the class of sulfonamides, with the exception of sulfanilamides (e.g., sulfamethoxazole).
Trial locations and contacts
77 sites in 7 countries.
77 sites in 7 countries
United States32 sites
Atlanta Cancer Care
Alpharetta, Georgia, 30005
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109
Fox Valley Hematology and Oncology, SC
Appleton, Wisconsin, 54915
Northside Hospital, Inc.-Georgia Cancer Specialists
Athens, Georgia, 30606
Atlanta Cancer Care
Atlanta, Georgia, 30342
Northside Hospital, Inc.
Atlanta, Georgia, 30342
CBCC Global Research a Comprehensive Blood and Cancer Center
Bakersfield, California, 93309
Overlake Medical Center
Bellevue, Washington, 98004
Northside Hospital, Inc.-Georgia Cancer Specialists
Canton, Georgia, 30114
Waverly Hematology Oncology
Cary, North Carolina, 27518
Tennessee Oncology PLLC
Chattanooga, Tennessee, 37404
Swedish Covenant
Chicago, Illinois, 60625
Atlanta Cancer Care
Conyers, Georgia, 30094
Atlanta Cancer Care
Cumming, Georgia, 30041
Florida Cancer Specialists
Daytona Beach, Florida, 32117
Atlanta Cancer Care
Decatur, Georgia, 30033
Northside Hospital, Inc.-Georgia Cancer Specialists
Decatur, Georgia, 30033
Hematology and Oncology Associates of Northeast PA
Dunmore, Pennsylvania, 18512
MD Anderson Cancer Center
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
Atlanta Cancer Care
Jonesboro, Georgia, 30236
Northside Hospital, Inc.-Georgia Cancer Specialists
Macon, Georgia, 31217
Northside Hospital, Inc.-Georgia Cancer Specialists
Marietta, Georgia, 30060
Southern Cancer Center
Mobile, Alabama, 36608
Summit Medical Group
Morristown, New Jersey, 07960
Southeastern Regional Medical Center
Newnan, Georgia, 30265
Mid Illinois Hematology & Oncology Associates, Ltd.
Normal, Illinois, 61761
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Northside Hospital, Inc.-Georgia Cancer Specialists
Sandy Springs, Georgia, 30342
Regional Cancer Care Associates
Sparta, New Jersey, 07871
Florida Cancer Specialists
West Palm Beach, Florida, 33401
Italy12 sites
Ospedale "Di Summa-Perrino"
Brindisi, 72100
Azienda Ospedaliero-Universitaria
Cagliari, 09042
Azienda Ospedaliero - Universitaria, Policlinico Vittorio Emanuele
Catania, 95123
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47014
Ospedale dell'Angelo
Mestre, 30174
Istituto Europeo di Oncologia
Milan, 20141
Azienda Ospedaliera, Ospedale San Carlo Borromeo
Milan, 20153
Fondazione IRCCS Policlinico S. Matteo
Pavia, 27100
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Pesaro, 61122
Nuovo Ospedale
Prato, 59100
Azienda Opspedaliero Universitaria Santa Maria della Misericordia
Udine, 33100
Ospedale SS Giovanni e Paolo
Venezia, 30122
France8 sites
Centre Paul Papin
Angers, 49000
Centre François Baclesse
Caen, 14000
Centre hospitalier de Saint-Brieuc, Yves Le Foll
La Roche-sur-Yon, 85925
Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren
Limoges, 87000
Institut Paoli Calmettes
Marseille, 13009
Centre Antoine Lacassagne
Nice, 06100
Hôpital Européen Georges Pompidou
Paris, 75015
Medicale Centre René Gauducheau
Saint-Herblain, 44805
Czechia7 sites
Masaryk Memorial Cancer Institute
Brno, 65653
Nemocnice Horovice a.s.
Hořovice, 26831
Fakultni nemocnice Hradec Králové
Hradec Králové, 50005
Fakultní nemocnice Královské Vinohrady
Prague, 10034
Onkologická klinika VFN a 1.LF UK
Prague, 12808
Fakultní nemocnice v Motole, Onkologická klinika 2. LF UK a FN Motol
Prague, 15006
Krajská nemocnice T.Bati, a. s.
Zlín, 76275
Spain7 sites
Centro Oncológico Regional de Galicia, Servicio de Oncologia Medica
A Coruña, Galicia, 15009
Complejo Hospitalario Universitario La Coruña
A Coruña, 15006
Hospital del Mar
Barcelona, 08003
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
Madrid, 28050
C. Hospital Xeral-Cies
Vigo, 36204
Poland6 sites
Bialostockie Centrum Onkologii im. Marii Sklodowskiej - Curie
Bialystok, 15001
Wojewódzkie Centrum Onkologii
Gdansk, 80219
Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli
Lublin, 20090
Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
Poznan, 61701
Mrukmed. Lekarz Beata Madej Mruk i Partner. Spólka Partnerska Oddzial nr 1 w Rzeszowie
Rzeszów, 35085
Magodent Sp. z o. o.
Warsaw, 04125
Belgium5 sites
Algemeen Ziekenhuis Klina
Brasschaat, 2930
Cliniques Universitaires Saint- LUC UCL
Brussels, 1200
Universitair Ziekenhuis Antwerpen
Edegem, 2650
CHU Ambroise Paré
Mons, 7000
AZ St Elisabeth
Namur, 5000
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Phase 2 Study of Paclitaxel in Combination With Reparixin Compared to Paclitaxel Alone as Front-line Therapy for Metastatic Triple- Negative Breast Cancer (FRIDA)
The Objectives of this study:
The primary objective of the study was to evaluate progression-free survival (PFS) (defined as the number of days between the date of randomization and the date of clinical disease progression (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, as assessed by Independent Radiology Review, or death for any cause, whichever occured first) in patients with metastatic triple-negative breast cancer (TNBC) treated with the combination of paclitaxel and orally administered reparixin compared to paclitaxel alone.
Read more
The secondary objectives were:
- To determine overall survival (OS).
- To evaluate objective response rates (ORR).
- To determine median PFS (mPFS).
- To assess the safety of the combination of paclitaxel and orally administered reparixin (referred to as combination treatment).
Read the detailed description
The study is a two arm, phase 2 study to evaluate the efficacy of the combination of paclitaxel and reparixin compared to paclitaxel and placebo in metastatic TNBC patients.
In the study two groups There were two groups:
Group 1: paclitaxel 80 mg/m2 intravenous (i.v.) (Days 1, 8, and 15 of 28-day cycle) + reparixin oral tablets 1200 mg three times a day (t.i.d.) continuing from Day 1 to Day 21.
Group 2: paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + placebo oral tablets 1200 mg t.i.d. continuing from Day 1 to Day 21.
Study drug (reparixin/placebo) was administered with water prior to the start of the i.v. paclitaxel infusion on Cycle 1, Day 1 and then administered approximately every eight hours (six to ten hours) for 21 consecutive days during each cycle with seven days off-treatment between each cycle. It was preferable that reparixin was taken with food. However, if the patient was unable to eat, study drug was allowed to be administered. When in combination with paclitaxel (Day 1, 8 and 15 of each cycle), reparixin or placebo was administered every approximately eight hours with about 250 mL water and a light meal or snack. Paclitaxel was administered in combination with study drug (reparixin/placebo) as an i.v. infusion on Days 1, 8 and 15 of each 28-day cycle.
On Cycle 1, Day 1, paclitaxel was administered at the clinic after the administration of study drug (reparixin/placebo). From that point forward, study drug (reparixin/placebo) was self-administered t.i.d. for 21 days. Combination treatment (three weeks on and one week off) continued until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
The next clinic visits were on Days 8 and 15 when a paclitaxel infusion was administered to the patient. The patients returned to the clinic again on Day 29/Day 1 of the next cycle.
Tumor response and/or progression assessments were performed and documented every eight weeks according to RECIST criteria version 1.1. Metastatic tissue samples were analyzed for evaluation of CD24-CD44+ and aldehyde dehydrogenase positive (ALDH+) CSCs.
- Conditions
- Metastatic Breast Cancer
- Being tested
- paclitaxel, Reparixin, placebo
- Keywords
- Triple negative metastatic breast cancer, Cancer Stem Cells
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
paclitaxelDrug
paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15)
ReparixinDrug
Also called REP
reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle
placeboDrug
placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| paclitaxel+reparixin | Experimental | paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d.
continuing from D 1 to Day 21 of 28-day cycle Receives: Drug: paclitaxel; Drug: Reparixin |
| paclitaxel+placebo | Active comparator | paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle Receives: Drug: paclitaxel; Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS was defined as the number of days between the date of randomization and the date of clinical disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first.
Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.
Measured: Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days
Secondary outcomes (7)
Overall Survival (OS)
OS was defined as the time from randomization until death due to any cause. For patients who did not die, time of death was censored at the date of last contact.
Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.
Measured: Baseline until death due to any cause, up to 985 days
Objective Response Rate (ORR)
The ORR was defined as the percentage of patients achieving CR or PR in the Evaluable Population. The response rate was calculated from the independently reviewed assessment best response. In case of PR or CR, only confirmed cases were considered to be responses.
Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Patients with unknown or missing response, including response of "not all evaluated" or "unable to determine", were treated as non-responders; i.e., they were included in the denominator when calculating the percentages.
Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.
Measured: Baseline up to every 8 weeks until documented disease progression, up to 56 months
Median Progression-free Survival (mPFS)
PFS was defined as the time from randomization to first documentation of disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first. For each treatment group, the Kaplan-Meier estimates for the median PFS time, the first and third quartiles were presented, along with approximate 95% confidence intervals if there were a sufficient number of progressions or deaths.
Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.
Measured: At screening and every 8 weeks, up to 721 days
Duration of Overall Response (DOR)
Duration of overall response (DOR) in days for the investigator assessments is measured from the time response criteria are first met for CR or PR (whichever is first recorded on the "Disease Response" page on the CRF) until either death or the first date that recurrent or PD is objectively documented (on the "Disease Response" p. on the CRF or the Follow-Up Disease Evaluation page indicates disease progression and there is supporting information in the Disease Status pages) per RECIST version 1.1. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. If a patient is lost to follow-up with no documentation of PD, DOR was censored at the last evaluable tumor assessment. DOR was calculated only for responding patients (PR or CR) as recorded on the CRF page "Disease Response" based upon the RECIST version 1.1.
Duration of overall response wa
Measured: Baseline up to every 8 weeks until documented disease progression, up to 557 days
Best Overall Response (BOR)
BOR is defined as the best response among all overall responses (in the order complete response [CR], partial response [PR], stable disease [SD], and progressive disease [PD]) recorded as an independent review response from the start of reparixin or placebo until disease progression/recurrence or end of treatment, or death, whichever comes first. The status of BOR of PR or CR needs to be confirmed by repeat tumor assessment within no less than 4 weeks according to RECIST version 1.1. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. If the status of CR or PR cannot be confirmed by repeat tumor assessment, the best overall response of unconfirmed CR and PR will be PR and SD, respectively. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.
Measured: From the start of treatment, every 8 weeks, up to 56 months
Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade
Treatment-emergent adverse events (TEAEs) are those which first occur or increase in severity or relationship to study drug after the first dose of study drug and before 30 days after the last dose of study treatment, reparixin/placebo. In the case of missing or partial dates, any AE that could have started on or after first dose date was assumed to be treatment-emergent. In the case of missing or partial dates, imputed dates (see section 10.1 AE date imputation) were used.
Measured: Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days
Serious AEs and Fatal AEs
A serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose
- - results in death, (fatal)
- - is life-threatening
- - requires inpatient hospitalization or causes prolongation of existing hospitalization
- - results in persistent or significant disability/incapacity,
- - may have caused a congenital anomaly/birth defect, or
- - requires intervention to prevent permanent impairment or damage.
Measured: Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2015 (estimated)
- Study start29 Jul 2015
- Primary completion20 Feb 2019
- Study completion23 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Metastatic 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 194 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dompé Farmaceutici S.p.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Lori J Goldstein, MD, Principal investigator, FASCOFox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02370238
- Sponsor's protocol ID
- REP0114
- Other IDs
- 2014-004796-23, 2014
- Acronym
- FRIDA
- Status last verified
- Aug 2022
- First submitted
- 11 Feb 2015
- Last updated
- 16 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cai S, Wei X, Li Q, Jiang Z, Li L. Smart materials in pharmacological drug development: Neutrophils and its constituents for drug delivery and consequent antitumor effects. Mol Immunol. 2025 Jul;183:18-32. doi: 10.1016/j.molimm.2025.04.010. Epub 2025 May 2.
PubMed 40318595Gong YT, Zhang LJ, Liu YC, Tang M, Lin JY, Chen XY, Chen YX, Yan Y, Zhang WD, Jin JM, Luan X. Neutrophils as potential therapeutic targets for breast cancer. Pharmacol Res. 2023 Dec;198:106996. doi: 10.1016/j.phrs.2023.106996. Epub 2023 Nov 14.
PubMed 37972723Schott AF, Goldstein LJ, Cristofanilli M, Ruffini PA, McCanna S, Reuben JM, Perez RP, Kato G, Wicha M. Phase Ib Pilot Study to Evaluate Reparixin in Combination with Weekly Paclitaxel in Patients with HER-2-Negative Metastatic Breast Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5358-5365. doi: 10.1158/1078-0432.CCR-16-2748. Epub 2017 May 24.
PubMed 28539464
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Phase 2 Study of Paclitaxel in Combination With Reparixin Compared to Paclitaxel Alone as Front-line Therapy for Metastatic Triple- Negative Breast Cancer (FRIDA)
- ClinicalTrials.gov ID
- NCT02370238
- Acronym / sponsor ID
- FRIDA / REP0114
- Conditions
- Metastatic Breast Cancer
- Keywords
- Triple negative metastatic breast cancer, Cancer Stem Cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 194 participants (actual)
- Lead sponsor
- Dompé Farmaceutici S.p.AIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 29 Jul 2015 (actual)
- Primary completion
- 20 Feb 2019 (actual)
- Study completion
- 23 Mar 2020 (actual)
- First posted
- 24 Feb 2015 (estimated)
- Results
- Posted 2 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Objectives of this study:
The primary objective of the study was to evaluate progression-free survival (PFS) (defined as the number of days between the date of randomization and the date of clinical disease progression (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, as assessed by Independent Radiology Review, or death for any cause, whichever occured first) in patients with metastatic triple-negative breast cancer (TNBC) treated with the combination of paclitaxel and orally administered reparixin compared to paclitaxel alone.
The secondary objectives were:
- To determine overall survival (OS).
- To evaluate objective response rates (ORR).
- To determine median PFS (mPFS).
- To assess the safety of the combination of paclitaxel and orally administered reparixin (referred to as combination treatment).
Detailed description
The study is a two arm, phase 2 study to evaluate the efficacy of the combination of paclitaxel and reparixin compared to paclitaxel and placebo in metastatic TNBC patients.
In the study two groups There were two groups:
Group 1: paclitaxel 80 mg/m2 intravenous (i.v.) (Days 1, 8, and 15 of 28-day cycle) + reparixin oral tablets 1200 mg three times a day (t.i.d.) continuing from Day 1 to Day 21.
Group 2: paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + placebo oral tablets 1200 mg t.i.d. continuing from Day 1 to Day 21.
Study drug (reparixin/placebo) was administered with water prior to the start of the i.v. paclitaxel infusion on Cycle 1, Day 1 and then administered approximately every eight hours (six to ten hours) for 21 consecutive days during each cycle with seven days off-treatment between each cycle. It was preferable that reparixin was taken with food. However, if the patient was unable to eat, study drug was allowed to be administered. When in combination with paclitaxel (Day 1, 8 and 15 of each cycle), reparixin or placebo was administered every approximately eight hours with about 250 mL water and a light meal or snack. Paclitaxel was administered in combination with study drug (reparixin/placebo) as an i.v. infusion on Days 1, 8 and 15 of each 28-day cycle.
On Cycle 1, Day 1, paclitaxel was administered at the clinic after the administration of study drug (reparixin/placebo). From that point forward, study drug (reparixin/placebo) was self-administered t.i.d. for 21 days. Combination treatment (three weeks on and one week off) continued until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
The next clinic visits were on Days 8 and 15 when a paclitaxel infusion was administered to the patient. The patients returned to the clinic again on Day 29/Day 1 of the next cycle.
Tumor response and/or progression assessments were performed and documented every eight weeks according to RECIST criteria version 1.1. Metastatic tissue samples were analyzed for evaluation of CD24-CD44+ and aldehyde dehydrogenase positive (ALDH+) CSCs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| paclitaxel+reparixin | Experimental | Drug: paclitaxel, Drug: Reparixinpaclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle |
| paclitaxel+placebo | Active comparator | Drug: paclitaxel, Drug: placebopaclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 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 (17 listed)
- Female aged ≥ 18 years.
- Patients with pathologically documented metastatic triple negative breast cancer (TNBC), eligible for treatment with paclitaxel. Paraffin-embedded tissue must be available from metastatic sites, if reasonably accessible, or from the primary tumor, to confirm the diagnosis of TNBC and for correlative studies (only on metastatic tissue). Fifteen slides can be obtained if the full block is not available to be sent or released.
- TNBC will be defined as breast cancer with <1% ER+ and <1% PgR+ cells, and HER2 immunohistochemistry score of 0 or 1+ and/or in situ hybridization (ISH) with HER2 gene copy number <4 or a ratio of less than 2 between HER2 gene copy number and centromere of chromosome 17. Patients whose metastatic disease is TNBC are eligible even when their primary tumor expressed hormone receptors and/or HER2.
- Patients must be newly diagnosed metastatic or must have relapsed following a prior (neo)adjuvant chemotherapy regimen. If a taxane (i.e., paclitaxel or docetaxel) was administered as part of the (neo)adjuvant regimen, PD must have occurred > 12 months from the end of previous (neo)adjuvant treatment. For non-taxane (neo)adjuvant regimen, PD must have occurred > 6 months from the end of previous (neo)adjuvant treatment
- Patients with at least one baseline measurable lesion according to RECIST criteria version 1.1.
Key exclusion criteria (12 listed)
- Prior therapy for metastatic TNBC (chemotherapy, hormone therapy or biological therapy), Patients may receive bisphosphonates and other therapies to treat bone metastases, however if used, bone lesions will not be considered as measurable disease.
- Less than four weeks since last radiotherapy (excluding palliative radiotherapy).
- Pregnancy or lactation or unwillingness to use adequate method of birth control.
- Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.
- Active or uncontrolled infection.
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 |
|---|---|---|
| paclitaxelpaclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) | Drug | paclitaxel+placebo, paclitaxel+reparixin |
| ReparixinAlso: REPreparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle | Drug | paclitaxel+reparixin |
| placeboplacebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle | Drug | paclitaxel+placebo |
Primary outcome
Progression Free Survival (PFS)
Time frame: Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days
PFS was defined as the number of days between the date of randomization and the date of clinical disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.
7 secondary outcomes
Overall Survival (OS)
Time frame: Baseline until death due to any cause, up to 985 days
Objective Response Rate (ORR)
Time frame: Baseline up to every 8 weeks until documented disease progression, up to 56 months
Median Progression-free Survival (mPFS)
Time frame: At screening and every 8 weeks, up to 721 days
Duration of Overall Response (DOR)
Time frame: Baseline up to every 8 weeks until documented disease progression, up to 557 days
Best Overall Response (BOR)
Time frame: From the start of treatment, every 8 weeks, up to 56 months
Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade
Time frame: Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days
Serious AEs and Fatal AEs
Time frame: Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40318595Cai S, Wei X, Li Q, Jiang Z, Li L. Smart materials in pharmacological drug development: Neutrophils and its constituents for drug delivery and consequent antitumor effects. Mol Immunol. 2025 Jul;183:18-32. doi: 10.1016/j.molimm.2025.04.010. Epub 2025 May 2.
- Derived from this study: PubMed 37972723Gong YT, Zhang LJ, Liu YC, Tang M, Lin JY, Chen XY, Chen YX, Yan Y, Zhang WD, Jin JM, Luan X. Neutrophils as potential therapeutic targets for breast cancer. Pharmacol Res. 2023 Dec;198:106996. doi: 10.1016/j.phrs.2023.106996. Epub 2023 Nov 14.
- Derived from this study: PubMed 28539464Schott AF, Goldstein LJ, Cristofanilli M, Ruffini PA, McCanna S, Reuben JM, Perez RP, Kato G, Wicha M. Phase Ib Pilot Study to Evaluate Reparixin in Combination with Weekly Paclitaxel in Patients with HER-2-Negative Metastatic Breast Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5358-5365. doi: 10.1158/1078-0432.CCR-16-2748. Epub 2017 May 24.
- Corporate webpageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Lori J Goldstein, MD principal investigator
FASCOFox Chase Cancer Center
77 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing paclitaxel and Reparixin in people with Metastatic Breast Cancer, run by Dompé Farmaceutici S.p.A at 77 sites in 7 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 17 inclusion and 12 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: finished, as of the sponsor's last update on 16 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 77 sites in United States, Italy, France, Czechia, Spain and 2 more countries. 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 2 Jun 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?
Progression Free Survival (PFS) (time frame: Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02370238, which also lists 3 linked publications.
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 16 Sep 2022.