FRIDA: A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer

• Sponsor: Dompé Farmaceutici S.p.A (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02370238
• Collaborator: PRA Health Sciences (Industry)
• Enrollment: 194
• Locations: 77
• Arms: 2
• Actual Duration (Months): 55.8
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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 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).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: paclitaxel; Drug: Reparixin; Drug: placebo	Phase 2

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

• Study Type: Interventional
• Actual Enrollment: 194 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Jul 29, 2015
• Actual Primary Completion Date: Feb 20, 2019
• Actual Study Completion Date: Mar 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: paclitaxel+reparixin 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	Drug: paclitaxel; paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15); Drug: Reparixin; reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle; Other Names: REP
Active Comparator: paclitaxel+placebo 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	Drug: paclitaxel; paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15); Drug: placebo; placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [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.

Secondary Outcome Measures

1. Overall Survival (OS) [Baseline until death due to any cause, up to 985 days]

   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.

2. Objective Response Rate (ORR) [Baseline up to every 8 weeks until documented disease progression, up to 56 months]

   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.

3. Median Progression-free Survival (mPFS) [At screening and every 8 weeks, up to 721 days]

   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.

4. Duration of Overall Response (DOR) [Baseline up to every 8 weeks until documented disease progression, up to 557 days]

   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

5. Best Overall Response (BOR) [From the start of treatment, every 8 weeks, up to 56 months]

   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.

6. Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade [Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days]

   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.

7. Serious AEs and Fatal AEs [Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Female aged ≥ 18 years.

2. 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.

1. 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

2. Patients with at least one baseline measurable lesion according to RECIST criteria version 1.1.

3. Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0-1.

4. Life expectancy of at least three months.

5. Patients must be able to swallow and retain oral medication (intact tablet).

6. Able to undergo all screening assessments outlined in the protocol.

7. Adequate organ function (defined by the following parameters):

8. Serum creatinine < 140 μmol/L (< 1.6 mg/dL) or creatinine clearance > 60 mL/min.

9. Serum hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L.

10. Serum bilirubin ≤ 1.5 x upper normal limit (UNL) except patients with Gilbert's syndrome

11. 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.

12. No history or evidence by CT scan or MRI, of brain metastases or leptomeningeal disease.

13. No known hepatitis B virus (not due to immunization), hepatitis C virus, human immunodeficiency virus-I and -II positive status.

14. Dated and signed IEC/IRB-approved informed consent.

Exclusion Criteria:

1. 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.

2. Less than four weeks since last radiotherapy (excluding palliative radiotherapy).

3. Pregnancy or lactation or unwillingness to use adequate method of birth control.

4. Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.

5. Active or uncontrolled infection.

6. Malabsorption syndrome, disease significantly affecting gastrointestinal function.

7. G>1 pre-existing peripheral neuropathy

8. 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

9. Hypersensitivity to:

10. paclitaxel

11. ibuprofen or to more than one non-steroidal anti-inflammatory drug.

12. medications belonging to the class of sulfonamides, with the exception of sulfanilamides (e.g., sulfamethoxazole).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Cancer Center	Mobile	Alabama	United States	36608
2	CBCC Global Research a Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309
3	Florida Cancer Specialists	Daytona Beach	Florida	United States	32117
4	Florida Cancer Specialists	West Palm Beach	Florida	United States	33401
5	Atlanta Cancer Care	Alpharetta	Georgia	United States	30005
6	Northside Hospital, Inc.-Georgia Cancer Specialists	Athens	Georgia	United States	30606
7	Atlanta Cancer Care	Atlanta	Georgia	United States	30342
8	Northside Hospital, Inc.	Atlanta	Georgia	United States	30342
9	Northside Hospital, Inc.-Georgia Cancer Specialists	Canton	Georgia	United States	30114
10	Atlanta Cancer Care	Conyers	Georgia	United States	30094
11	Atlanta Cancer Care	Cumming	Georgia	United States	30041
12	Atlanta Cancer Care	Decatur	Georgia	United States	30033
13	Northside Hospital, Inc.-Georgia Cancer Specialists	Decatur	Georgia	United States	30033
14	Atlanta Cancer Care	Jonesboro	Georgia	United States	30236
15	Northside Hospital, Inc.-Georgia Cancer Specialists	Macon	Georgia	United States	31217
16	Northside Hospital, Inc.-Georgia Cancer Specialists	Marietta	Georgia	United States	30060
17	Southeastern Regional Medical Center	Newnan	Georgia	United States	30265
18	Northside Hospital, Inc.-Georgia Cancer Specialists	Sandy Springs	Georgia	United States	30342
19	Swedish Covenant	Chicago	Illinois	United States	60625
20	Mid Illinois Hematology & Oncology Associates, Ltd.	Normal	Illinois	United States	61761
21	University of Michigan Cancer Center	Ann Arbor	Michigan	United States	48109
22	Summit Medical Group	Morristown	New Jersey	United States	07960
23	Regional Cancer Care Associates	Sparta	New Jersey	United States	07871
24	Waverly Hematology Oncology	Cary	North Carolina	United States	27518
25	Hematology and Oncology Associates of Northeast PA	Dunmore	Pennsylvania	United States	18512
26	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
27	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
28	Tennessee Oncology PLLC	Chattanooga	Tennessee	United States	37404
29	MD Anderson Cancer Center	Houston	Texas	United States	77030
30	The Methodist Hospital	Houston	Texas	United States	77030
31	Overlake Medical Center	Bellevue	Washington	United States	98004
32	Fox Valley Hematology and Oncology, SC	Appleton	Wisconsin	United States	54915
33	Algemeen Ziekenhuis Klina	Brasschaat		Belgium	2930
34	Cliniques Universitaires Saint- LUC UCL	Brussels		Belgium	1200
35	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	2650
36	CHU Ambroise Paré	Mons		Belgium	7000
37	AZ St Elisabeth	Namur		Belgium	5000
38	Masaryk Memorial Cancer Institute	Brno		Czechia	65653
39	Nemocnice Horovice a.s.	Horovice		Czechia	26831
40	Fakultni nemocnice Hradec Králové	Hradec Králové		Czechia	50005
41	Onkologická klinika VFN a 1.LF UK	Prague 2		Czechia	12808
42	Fakultní nemocnice Královské Vinohrady	Praha 10		Czechia	10034
43	Fakultní nemocnice v Motole, Onkologická klinika 2. LF UK a FN Motol	Praha 5		Czechia	15006
44	Krajská nemocnice T.Bati, a. s.	Zlin		Czechia	76275
45	Centre Paul Papin	Angers		France	49000
46	Centre François Baclesse	Caen		France	14000
47	Centre hospitalier de Saint-Brieuc, Yves Le Foll	La Roche sur Yon Cedex 9		France	85925
48	Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren	Limoges		France	87000
49	Institut Paoli Calmettes	Marseille cedex 9		France	13009
50	Centre Antoine Lacassagne	Nice Cedex 2		France	06100
51	Hôpital Européen Georges Pompidou	Paris Cedex 15		France	75015
52	Medicale Centre René Gauducheau	Saint Herblain cedex		France	44805
53	Ospedale "Di Summa-Perrino"	Brindisi		Italy	72100
54	Azienda Ospedaliero-Universitaria	Cagliari		Italy	09042
55	Azienda Ospedaliero - Universitaria, Policlinico Vittorio Emanuele	Catania		Italy	95123
56	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola		Italy	47014
57	Ospedale dell'Angelo	Mestre		Italy	30174
58	Istituto Europeo di Oncologia	Milan		Italy	20141
59	Azienda Ospedaliera, Ospedale San Carlo Borromeo	Milan		Italy	20153
60	Fondazione IRCCS Policlinico S. Matteo	Pavia		Italy	27100
61	Azienda Ospedaliera Ospedali Riuniti Marche Nord	Pesaro		Italy	61122
62	Nuovo Ospedale	Prato		Italy	59100
63	Azienda Opspedaliero Universitaria Santa Maria della Misericordia	Udine		Italy	33100
64	Ospedale SS Giovanni e Paolo	Venezia		Italy	30122
65	Bialostockie Centrum Onkologii im. Marii Sklodowskiej - Curie	Bialystok		Poland	15001
66	Wojewódzkie Centrum Onkologii	Gdansk		Poland	80219
67	Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli	Lublin		Poland	20090
68	Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu	Poznan		Poland	61701
69	Mrukmed. Lekarz Beata Madej Mruk i Partner. Spólka Partnerska Oddzial nr 1 w Rzeszowie	Rzeszów		Poland	35085
70	Magodent Sp. z o. o.	Warsaw		Poland	04125
71	Centro Oncológico Regional de Galicia, Servicio de Oncologia Medica	La Coruña	Galizia	Spain	15009
72	Hospital del Mar	Barcelona		Spain	08003
73	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
74	Complejo Hospitalario Universitario La Coruña	La Coruña		Spain	15006
75	Hospital General Universitario Gregorio Marañon	Madrid		Spain	28007
76	Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro	Madrid		Spain	28050
77	C. Hospital Xeral-Cies	Vigo		Spain	36204

Sponsors and Collaborators

• Dompé Farmaceutici S.p.A
• PRA Health Sciences

Investigators

• Principal Investigator: Lori J Goldstein, MD, FASCOFox Chase Cancer Center

Study Documents (Full-Text)

• Study Protocol - Nov 25, 2019
• Statistical Analysis Plan - May 30, 2019

More Information

Additional Information:

• Corporate webpage

Publications

None provided.

• Responsible Party: Dompé Farmaceutici S.p.A
• ClinicalTrials.gov Identifier: NCT02370238
• Other Study ID Numbers: REP0114; 2014-004796-23
• First Posted: Feb 24, 2015
• Last Update Posted: Jun 2, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Dompé Farmaceutici S.p.A: Triple negative metastatic breast cancer; Cancer Stem Cells
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms; Paclitaxel

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	Paclitaxel+Reparixin (Group 1)	Paclitaxel+Placebo (Group 2)
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	62	61
ITT Population	62	61
Safety Population	61	60
Responsable-evaluable Population	57	54
COMPLETED	15	16
NOT COMPLETED	47	45

Baseline Characteristics

Arm/Group Title	Paclitaxel+Reparixin (Group 1) - Safety Population	Paclitaxel+Placebo (Group 2) - Safety Population	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	61	60	121
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	44 72.1%	44 73.3%	88 72.7%
>=65 years	17 27.9%	16 26.7%	33 27.3%
Sex: Female, Male (Count of Participants)
Female	61 100%	60 100%	121 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 4.9%	2 3.3%	5 4.1%
Not Hispanic or Latino	48 78.7%	54 90%	102 84.3%
Unknown or Not Reported	10 16.4%	4 6.7%	14 11.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 1.7%	1 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 9.8%	6 10%	12 9.9%
White	45 73.8%	49 81.7%	94 77.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	10 16.4%	4 6.7%	14 11.6%
Region of Enrollment (participants) [Number]
Belgium	4 6.6%	6 10%	10 8.3%
United States	15 24.6%	19 31.7%	34 28.1%
Czechia	3 4.9%	8 13.3%	11 9.1%
Poland	6 9.8%	3 5%	9 7.4%
Italy	16 26.2%	12 20%	28 23.1%
France	10 16.4%	4 6.7%	14 11.6%
Spain	7 11.5%	8 13.3%	15 12.4%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	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.
Time Frame	Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Paclitaxel+Reparixin (Group 1) - ITT Population	Paclitaxel+Placebo (Group 2)
Arm/Group Description	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.	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.
Measure Participants	62	61
Median (Inter-Quartile Range) [Days]	166	171

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel+Reparixin (Group 1) - ITT Population, Paclitaxel+Placebo (Group 2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.589
	Comments	p-value based on a log-rank test stratified by randomized sub-populations, newly diagnosed metastatic patients and patients that had relapsed following a prior (neo)adjuvant chemotherapy regimen.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	Baseline until death due to any cause, up to 985 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Paclitaxel+Reparixin (Group 1) - ITT Population	Paclitaxel+Placebo (Group 2)
Arm/Group Description	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.	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.
Measure Participants	62	61
Median (Inter-Quartile Range) [Days]	483	531

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel+Reparixin (Group 1) - ITT Population, Paclitaxel+Placebo (Group 2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.897
	Comments	p-value based on a log-rank test stratified by randomized sub-populations, newly diagnosed metastatic patients and patients that had relapsed following a prior (neo)adjuvant chemotherapy regimen.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	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.
Time Frame	Baseline up to every 8 weeks until documented disease progression, up to 56 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Paclitaxel+Reparixin (Group 1) - ITT Population	Paclitaxel+Placebo (Group 2)
Arm/Group Description	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.	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.
Measure Participants	57	54
Number (95% Confidence Interval) [Percentage of patients]	28.1	25.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel+Reparixin (Group 1) - ITT Population, Paclitaxel+Placebo (Group 2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.667
	Comments	P-value is based on Zelen's test for homogeneity of the odds ratios.
	Method	Zelen's test
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.262
	Confidence Interval	(2-Sided) 95%; 0.4909 to 3.963
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Median Progression-free Survival (mPFS)
Description	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.
Time Frame	At screening and every 8 weeks, up to 721 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Paclitaxel+Reparixin (Group 1) - ITT Population	Paclitaxel+Placebo (Group 2)
Arm/Group Description	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.	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.
Measure Participants	62	61
Median (95% Confidence Interval) [Days]	166	171

5. Secondary Outcome

Title	Duration of Overall Response (DOR)
Description	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
Time Frame	Baseline up to every 8 weeks until documented disease progression, up to 557 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Group 1 - Response Evaluable Population	Group 2 - Response-Evaluable Population
Arm/Group Description	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.	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.
Measure Participants	57	54
Median (Inter-Quartile Range) [Days]	293.0	172.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel+Reparixin (Group 1) - ITT Population, Paclitaxel+Placebo (Group 2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.519
	Comments	For the All Patients group, p-value was based on a log-rank test stratified by actual sub-populations, newly diagnosed metastatic patients and patients that had relapsed following a prior (neo)adjuvant chemotherapy regimen.
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Best Overall Response (BOR)
Description	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.
Time Frame	From the start of treatment, every 8 weeks, up to 56 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Group 1 - Response Evaluable Population	Group 2 - Response-Evaluable Population
Arm/Group Description	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.	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.
Measure Participants	57	54
CR	1 1.6%	0 0%
PR	15 24.6%	14 23.3%
SD	16 26.2%	23 38.3%
PD	22 36.1%	14 23.3%
NE	3 4.9%	3 5%
Unable to determine	0 0%	0 0%
Unknown/not done	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel+Reparixin (Group 1) - ITT Population, Paclitaxel+Placebo (Group 2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.667
	Comments	P-value was based on Zelen's test for homogeneity of the odds ratios
	Method	Zelen's test
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.101
	Confidence Interval	(2-Sided) 95%; 0.437 to 2.790
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade
Description	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.
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Paclitaxel+Reparixin (Group 1) - Safety Population	Paclitaxel+Placebo (Group 2) - Safety Population
Arm/Group Description	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.	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.
Measure Participants	61	60
Overall	865	730
Grade 1 (mild)	563	478
Grade 2 (moderate)	230	194
Grade 3 (severe)	67	50
Grade 4 (Life-threatening or disabling)	2	4
Grade 5 (death)	3	4

8. Secondary Outcome

Title	Serious AEs and Fatal AEs
Description	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.
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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Paclitaxel+Reparixin (Group 1) - Safety Population	Paclitaxel+Placebo (Group 2) - Safety Population
Arm/Group Description	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.	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.
Measure Participants	61	60
serious AE	31	25
Fatal AE	3	4

Adverse Events

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.
Arm/Group Title	Paclitaxel+Reparixin (Group 1) - Safety Population		Paclitaxel+Placebo (Group 2) - Safety Population
Arm/Group Description	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.		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.
All Cause Mortality
	Paclitaxel+Reparixin (Group 1) - Safety Population		Paclitaxel+Placebo (Group 2) - Safety Population
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/61 (68.9%)		35/60 (58.3%)
Serious Adverse Events
	Paclitaxel+Reparixin (Group 1) - Safety Population		Paclitaxel+Placebo (Group 2) - Safety Population
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/61 (21.3%)		12/60 (20%)
Blood and lymphatic system disorders
Anaemia	1/61 (1.6%)	1	1/60 (1.7%)	1
Febrile neutropenia	1/61 (1.6%)	1	0/60 (0%)	0
Cardiac disorders
Cardiac failure congestive	0/61 (0%)	0	1/60 (1.7%)	1
Pericardial effusion	0/61 (0%)	0	1/60 (1.7%)	1
Gastrointestinal disorders
Constipation	1/61 (1.6%)	1	0/60 (0%)	0
Intestinal perforation	1/61 (1.6%)	1	0/60 (0%)	0
Stomatitis	0/61 (0%)	0	1/60 (1.7%)	1
General disorders
Non-cardiac chest pain	2/61 (3.3%)	2	0/60 (0%)	0
Condition aggravated	1/61 (1.6%)	1	0/60 (0%)	0
General physical health deterioration	1/61 (1.6%)	1	1/60 (1.7%)	1
Pyrexia	1/61 (1.6%)	1	0/60 (0%)	0
Asthenia	0/61 (0%)	0	1/60 (1.7%)	1
Disease progression	0/61 (0%)	0	1/60 (1.7%)	1
Infections and infestations
Erysipelas	1/61 (1.6%)	1	0/60 (0%)	0
Lung infection	1/61 (1.6%)	1	0/60 (0%)	0
Peritonitis	1/61 (1.6%)	1	0/60 (0%)	0
Pneumonia influenzal	1/61 (1.6%)	1	0/60 (0%)	0
Pneumonia	0/61 (0%)	0	1/60 (1.7%)	1
Sepsis	0/61 (0%)	0	1/60 (1.7%)	1
Injury, poisoning and procedural complications
Ankle fracture	0/61 (0%)	0	1/60 (1.7%)	1
Fall	0/61 (0%)	0	1/60 (1.7%)	1
Investigations
Alanine aminotransferase increased	1/61 (1.6%)	1	0/60 (0%)	0
Aspartate aminotransferase increased	1/61 (1.6%)	1	0/60 (0%)	0
Gamma-glutamyltransferase increased	1/61 (1.6%)	1	0/60 (0%)	0
Metabolism and nutrition disorders
Gout	1/61 (1.6%)	1	0/60 (0%)	0
Hyponatraemia	1/61 (1.6%)	1	0/60 (0%)	0
Hyperglycaemia	0/61 (0%)	0	1/60 (1.7%)	1
Presyncope	0/61 (0%)	0	1/60 (1.7%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/61 (1.6%)	1	0/60 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion	0/61 (0%)	0	1/60 (1.7%)	1
Metastases to central nervous system	0/61 (0%)	0	1/60 (1.7%)	1
Nervous system disorders
Myelopathy	1/61 (1.6%)	1	0/60 (0%)	0
Headache	0/61 (0%)	0	1/60 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/61 (3.3%)	2	0/60 (0%)	0
Pleural effusion	1/61 (1.6%)	1	0/60 (0%)	0
Haemothorax	0/61 (0%)	0	1/60 (1.7%)	1
Pulmonary embolism	0/61 (0%)	0	1/60 (1.7%)	1
Respiratory failure	0/61 (0%)	0	3/60 (5%)	3
Vascular disorders
Deep vein thrombosis	1/61 (1.6%)	1	0/60 (0%)	0
Embolism	1/61 (1.6%)	1	0/60 (0%)	0
Thrombosis	0/61 (0%)	0	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Paclitaxel+Reparixin (Group 1) - Safety Population		Paclitaxel+Placebo (Group 2) - Safety Population
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/61 (34.4%)		21/60 (35%)
Skin and subcutaneous tissue disorders
Alopecia	21/61 (34.4%)	26	21/60 (35%)	21

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.