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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-004796-23 | EudraCT Number |
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| Name | Class |
|---|---|
| PRA Health Sciences | INDUSTRY |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| paclitaxel | Drug | paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline until death due to any cause, up to 985 days |
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Inclusion Criteria:
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.
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):
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.
Exclusion Criteria:
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.
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:
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| Name | Affiliation | Role |
|---|---|---|
| Lori J Goldstein, MD | FASCOFox Chase Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Southern Cancer Center | Mobile | Alabama | 36608 | United States | ||
| CBCC Global Research a Comprehensive Blood and Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40318595 | Derived | 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. | |
| 37972723 | Derived | Gong 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. |
| Label | URL |
|---|---|
| Corporate webpage | View source |
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Due to extreme enrollment difficulties during the first 6 months of 2018, enrollment to the study was terminated early (30 July 2018) and the final sample size is equal to 123 randomized patients.
Of the 194 enrolled patients, 123 were randomized and included in the ITT Population: 62 patients in Group 1 and 61 patients in Group 2.
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| ID | Title | Description |
|---|---|---|
| FG000 | Paclitaxel+Reparixin (Group 1) | 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. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 25, 2019 | Feb 5, 2021 |
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| Reparixin | Drug | reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle |
|
|
| placebo | Drug | placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle |
|
| 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. | 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. | 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 | 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. | 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. | 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
| Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. |
| Bakersfield |
| California |
| 93309 |
| United States |
| Florida Cancer Specialists | Daytona Beach | Florida | 32117 | United States |
| Florida Cancer Specialists | West Palm Beach | Florida | 33401 | United States |
| Atlanta Cancer Care | Alpharetta | Georgia | 30005 | United States |
| Northside Hospital, Inc.-Georgia Cancer Specialists | Athens | Georgia | 30606 | United States |
| Atlanta Cancer Care | Atlanta | Georgia | 30342 | United States |
| Northside Hospital, Inc. | Atlanta | Georgia | 30342 | United States |
| Northside Hospital, Inc.-Georgia Cancer Specialists | Canton | Georgia | 30114 | United States |
| Atlanta Cancer Care | Conyers | Georgia | 30094 | United States |
| Atlanta Cancer Care | Cumming | Georgia | 30041 | United States |
| Atlanta Cancer Care | Decatur | Georgia | 30033 | United States |
| Northside Hospital, Inc.-Georgia Cancer Specialists | Decatur | Georgia | 30033 | United States |
| Atlanta Cancer Care | Jonesboro | Georgia | 30236 | United States |
| Northside Hospital, Inc.-Georgia Cancer Specialists | Macon | Georgia | 31217 | United States |
| Northside Hospital, Inc.-Georgia Cancer Specialists | Marietta | Georgia | 30060 | United States |
| Southeastern Regional Medical Center | Newnan | Georgia | 30265 | United States |
| Northside Hospital, Inc.-Georgia Cancer Specialists | Sandy Springs | Georgia | 30342 | United States |
| Swedish Covenant | Chicago | Illinois | 60625 | United States |
| Mid Illinois Hematology & Oncology Associates, Ltd. | Normal | Illinois | 61761 | United States |
| University of Michigan Cancer Center | Ann Arbor | Michigan | 48109 | United States |
| Summit Medical Group | Morristown | New Jersey | 07960 | United States |
| Regional Cancer Care Associates | Sparta | New Jersey | 07871 | United States |
| Waverly Hematology Oncology | Cary | North Carolina | 27518 | United States |
| Hematology and Oncology Associates of Northeast PA | Dunmore | Pennsylvania | 18512 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| Tennessee Oncology PLLC | Chattanooga | Tennessee | 37404 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| The Methodist Hospital | Houston | Texas | 77030 | United States |
| Overlake Medical Center | Bellevue | Washington | 98004 | United States |
| Fox Valley Hematology and Oncology, SC | Appleton | Wisconsin | 54915 | United States |
| Algemeen Ziekenhuis Klina | Brasschaat | 2930 | Belgium |
| Cliniques Universitaires Saint- LUC UCL | Brussels | 1200 | Belgium |
| Universitair Ziekenhuis Antwerpen | Edegem | 2650 | Belgium |
| CHU Ambroise Paré | Mons | 7000 | Belgium |
| AZ St Elisabeth | Namur | 5000 | Belgium |
| Masaryk Memorial Cancer Institute | Brno | 65653 | Czechia |
| Nemocnice Horovice a.s. | Hořovice | 26831 | Czechia |
| Fakultni nemocnice Hradec Králové | Hradec Králové | 50005 | Czechia |
| Fakultnà nemocnice Královské Vinohrady | Prague | 10034 | Czechia |
| Onkologická klinika VFN a 1.LF UK | Prague | 12808 | Czechia |
| Fakultnà nemocnice v Motole, Onkologická klinika 2. LF UK a FN Motol | Prague | 15006 | Czechia |
| Krajská nemocnice T.Bati, a. s. | ZlÃn | 76275 | Czechia |
| Centre Paul Papin | Angers | 49000 | France |
| Centre François Baclesse | Caen | 14000 | France |
| Centre hospitalier de Saint-Brieuc, Yves Le Foll | La Roche-sur-Yon | 85925 | France |
| Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren | Limoges | 87000 | France |
| Institut Paoli Calmettes | Marseille | 13009 | France |
| Centre Antoine Lacassagne | Nice | 06100 | France |
| Hôpital Européen Georges Pompidou | Paris | 75015 | France |
| Medicale Centre René Gauducheau | Saint-Herblain | 44805 | France |
| Ospedale "Di Summa-Perrino" | Brindisi | 72100 | Italy |
| Azienda Ospedaliero-Universitaria | Cagliari | 09042 | Italy |
| Azienda Ospedaliero - Universitaria, Policlinico Vittorio Emanuele | Catania | 95123 | Italy |
| Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Meldola | 47014 | Italy |
| Ospedale dell'Angelo | Mestre | 30174 | Italy |
| Istituto Europeo di Oncologia | Milan | 20141 | Italy |
| Azienda Ospedaliera, Ospedale San Carlo Borromeo | Milan | 20153 | Italy |
| Fondazione IRCCS Policlinico S. Matteo | Pavia | 27100 | Italy |
| Azienda Ospedaliera Ospedali Riuniti Marche Nord | Pesaro | 61122 | Italy |
| Nuovo Ospedale | Prato | 59100 | Italy |
| Azienda Opspedaliero Universitaria Santa Maria della Misericordia | Udine | 33100 | Italy |
| Ospedale SS Giovanni e Paolo | Venezia | 30122 | Italy |
| Bialostockie Centrum Onkologii im. Marii Sklodowskiej - Curie | Bialystok | 15001 | Poland |
| Wojewódzkie Centrum Onkologii | Gdansk | 80219 | Poland |
| Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli | Lublin | 20090 | Poland |
| Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu | Poznan | 61701 | Poland |
| Mrukmed. Lekarz Beata Madej Mruk i Partner. Spólka Partnerska Oddzial nr 1 w Rzeszowie | Rzeszów | 35085 | Poland |
| Magodent Sp. z o. o. | Warsaw | 04125 | Poland |
| Centro Oncológico Regional de Galicia, Servicio de Oncologia Medica | A Coruña | Galicia | 15009 | Spain |
| Complejo Hospitalario Universitario La Coruña | A Coruña | 15006 | Spain |
| Hospital del Mar | Barcelona | 08003 | Spain |
| Hospital Universitario Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital General Universitario Gregorio Marañon | Madrid | 28007 | Spain |
| Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro | Madrid | 28050 | Spain |
| C. Hospital Xeral-Cies | Vigo | 36204 | Spain |
| 28539464 | Derived | Schott 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. |
| FG001 | Paclitaxel+Placebo (Group 2) | 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. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. |
| ITT Population |
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| Safety Population |
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| Responsable-evaluable Population |
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| COMPLETED |
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| NOT COMPLETED |
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The Safety Population consisted of 121 patients who took at least one dose of study treatment
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Paclitaxel+Reparixin (Group 1) - Safety Population | 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. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. |
| BG001 | Paclitaxel+Placebo (Group 2) - Safety Population | 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. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population. | Posted | Median | Inter-Quartile Range | Days | Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days |
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| Secondary | 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. | The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population. | Posted | Median | Inter-Quartile Range | Days | Baseline until death due to any cause, up to 985 days |
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| Secondary | 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. | Responsible-evaluable population: this population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment. | Posted | Number | 95% Confidence Interval | Percentage of patients | Baseline up to every 8 weeks until documented disease progression, up to 56 months |
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| Secondary | 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. | The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population. | Posted | Median | 95% Confidence Interval | Days | At screening and every 8 weeks, up to 721 days |
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| Secondary | 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 | The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment. | Posted | Median | Inter-Quartile Range | Days | Baseline up to every 8 weeks until documented disease progression, up to 557 days |
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| Secondary | 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. | The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment. | Posted | Number | participants | From the start of treatment, every 8 weeks, up to 56 months |
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| Secondary | 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. | Safety population: this population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received. | Posted | Number | number of events | Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days |
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| Secondary | 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
| Safety population: this population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received. | Posted | Number | number of events | Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. |
|
Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days.
A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Paclitaxel+Reparixin (Group 1) - Safety Population | 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. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. | 42 | 61 | 13 | 61 | 60 | 61 |
| EG001 | Paclitaxel+Placebo (Group 2) - Safety Population | 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. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. | 35 | 60 | 12 | 60 | 57 | 60 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Erysipelas | Infections and infestations | MedDRA 20 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia influenzal | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Condition aggravated | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Haemothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20 | Systematic Assessment |
| |
| Intestinal perforation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Myelopathy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Presyncope | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Paresthesia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| insomnia | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Pier Adelchi Ruffini, MD | Dompé Farmaceutici SpA | +39 02 583831 | info@dompe.it |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 30, 2019 | Feb 2, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D017239 | Paclitaxel |
| C490707 | reparixin |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| United States |
|
| Czechia |
|
| Poland |
|
| Italy |
|
| France |
|
| Spain |
|
|
|
|
| OG001 | Paclitaxel+Placebo (Group 2) | 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. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. |
|
|
|
| Paclitaxel+Placebo (Group 2) |
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. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. |
|
|
| OG001 | Group 2 - Response-Evaluable Population | 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. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. |
|
|
|
| OG001 | Group 2 - Response-Evaluable Population | 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. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first. |
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