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

NCT02370238 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: REP01142014-004796-23
• Study Type: interventional
• Target: 194
• Locations: 7 countries
• Sites: 77

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).

Conditions

Metastatic Breast Cancer

Keywords

Triple negative metastatic breast cancer; Cancer Stem Cells

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• Overall Survival (OS)

  Baseline until death due to any cause, up to 985 days

• Objective Response Rate (ORR)

  Baseline up to every 8 weeks until documented disease progression, up to 56 months

• Median Progression-free Survival (mPFS)

  At screening and every 8 weeks, up to 721 days

• Duration of Overall Response (DOR)

  Baseline up to every 8 weeks until documented disease progression, up to 557 days

• Best Overall Response (BOR)

  From the start of treatment, every 8 weeks, up to 56 months

Study Arms (2)

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

Drug: paclitaxel; Drug: Reparixin

paclitaxel+placebo

ACTIVE COMPARATOR

paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle

Drug: paclitaxel; Drug: placebo

Interventions

paclitaxel DRUG

paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15)

paclitaxel+placebo; paclitaxel+reparixin

Reparixin DRUG

reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle

Also known as: REP

paclitaxel+reparixin

placebo DRUG

placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle

paclitaxel+placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Serum creatinine \< 140 μmol/L (\< 1.6 mg/dL) or creatinine clearance \> 60 mL/min.
• Serum hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L.
• Serum bilirubin ≤ 1.5 x upper normal limit (UNL) except patients with Gilbert's syndrome
• Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x UNL but ≤ 5.0 x UNL in case of liver metastases; alkaline phosphatase (ALP) ≤ UNL but i) ≤ 2.5 x UNL in case of liver metastases and ii) ≤ 5 UNL in case of bone metastases; albumin ≥ 2.5 g/dl.
• No history or evidence by CT scan or MRI, of brain metastases or leptomeningeal disease.

You may not qualify if:

• 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:
• paclitaxel
• ibuprofen or to more than one non-steroidal anti-inflammatory drug.
• medications belonging to the class of sulfonamides, with the exception of sulfanilamides (e.g., sulfamethoxazole).

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead
• PRA Health Sciences: collaborator

Study Sites (77)

Southern Cancer Center

Mobile, Alabama, 36608, United States

Location

CBCC Global Research a Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

Florida Cancer Specialists

Daytona Beach, Florida, 32117, United States

Location

Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

Location

Atlanta Cancer Care

Alpharetta, Georgia, 30005, United States

Location

Northside Hospital, Inc.-Georgia Cancer Specialists

Athens, Georgia, 30606, United States

Location

Atlanta Cancer Care

Atlanta, Georgia, 30342, United States

Location

Northside Hospital, Inc.

Atlanta, Georgia, 30342, United States

Location

Northside Hospital, Inc.-Georgia Cancer Specialists

Canton, Georgia, 30114, United States

Location

Atlanta Cancer Care

Conyers, Georgia, 30094, United States

Location

Atlanta Cancer Care

Cumming, Georgia, 30041, United States

Location

Atlanta Cancer Care

Decatur, Georgia, 30033, United States

Location

Northside Hospital, Inc.-Georgia Cancer Specialists

Decatur, Georgia, 30033, United States

Location

Atlanta Cancer Care

Jonesboro, Georgia, 30236, United States

Location

Northside Hospital, Inc.-Georgia Cancer Specialists

Macon, Georgia, 31217, United States

Location

Northside Hospital, Inc.-Georgia Cancer Specialists

Marietta, Georgia, 30060, United States

Location

Southeastern Regional Medical Center

Newnan, Georgia, 30265, United States

Location

Northside Hospital, Inc.-Georgia Cancer Specialists

Sandy Springs, Georgia, 30342, United States

Location

Swedish Covenant

Chicago, Illinois, 60625, United States

Location

Mid Illinois Hematology & Oncology Associates, Ltd.

Normal, Illinois, 61761, United States

Location

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Summit Medical Group

Morristown, New Jersey, 07960, United States

Location

Regional Cancer Care Associates

Sparta, New Jersey, 07871, United States

Location

Waverly Hematology Oncology

Cary, North Carolina, 27518, United States

Location

Hematology and Oncology Associates of Northeast PA

Dunmore, Pennsylvania, 18512, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Tennessee Oncology PLLC

Chattanooga, Tennessee, 37404, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

Overlake Medical Center

Bellevue, Washington, 98004, United States

Location

Fox Valley Hematology and Oncology, SC

Appleton, Wisconsin, 54915, United States

Location

Algemeen Ziekenhuis Klina

Brasschaat, 2930, Belgium

Location

Cliniques Universitaires Saint- LUC UCL

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

CHU Ambroise Paré

Mons, 7000, Belgium

Location

AZ St Elisabeth

Namur, 5000, Belgium

Location

Masaryk Memorial Cancer Institute

Brno, 65653, Czechia

Location

Nemocnice Horovice a.s.

Hořovice, 26831, Czechia

Location

Fakultni nemocnice Hradec Králové

Hradec Králové, 50005, Czechia

Location

Fakultní nemocnice Královské Vinohrady

Prague, 10034, Czechia

Location

Onkologická klinika VFN a 1.LF UK

Prague, 12808, Czechia

Location

Fakultní nemocnice v Motole, Onkologická klinika 2. LF UK a FN Motol

Prague, 15006, Czechia

Location

Krajská nemocnice T.Bati, a. s.

Zlín, 76275, Czechia

Location

Centre Paul Papin

Angers, 49000, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre hospitalier de Saint-Brieuc, Yves Le Foll

La Roche-sur-Yon, 85925, France

Location

Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren

Limoges, 87000, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Centre Antoine Lacassagne

Nice, 06100, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

Medicale Centre René Gauducheau

Saint-Herblain, 44805, France

Location

Ospedale "Di Summa-Perrino"

Brindisi, 72100, Italy

Location

Azienda Ospedaliero-Universitaria

Cagliari, 09042, Italy

Location

Azienda Ospedaliero - Universitaria, Policlinico Vittorio Emanuele

Catania, 95123, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Ospedale dell'Angelo

Mestre, 30174, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Azienda Ospedaliera, Ospedale San Carlo Borromeo

Milan, 20153, Italy

Location

Fondazione IRCCS Policlinico S. Matteo

Pavia, 27100, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, 61122, Italy

Location

Nuovo Ospedale

Prato, 59100, Italy

Location

Azienda Opspedaliero Universitaria Santa Maria della Misericordia

Udine, 33100, Italy

Location

Ospedale SS Giovanni e Paolo

Venezia, 30122, Italy

Location

Bialostockie Centrum Onkologii im. Marii Sklodowskiej - Curie

Bialystok, 15001, Poland

Location

Wojewódzkie Centrum Onkologii

Gdansk, 80219, Poland

Location

Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli

Lublin, 20090, Poland

Location

Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu

Poznan, 61701, Poland

Location

Mrukmed. Lekarz Beata Madej Mruk i Partner. Spólka Partnerska Oddzial nr 1 w Rzeszowie

Rzeszów, 35085, Poland

Location

Magodent Sp. z o. o.

Warsaw, 04125, Poland

Location

Centro Oncológico Regional de Galicia, Servicio de Oncologia Medica

A Coruña, Galicia, 15009, Spain

Location

Complejo Hospitalario Universitario La Coruña

A Coruña, 15006, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro

Madrid, 28050, Spain

Location

C. Hospital Xeral-Cies

Vigo, 36204, Spain

Location

Related Publications (2)

• 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.

  PMID: 37972723 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.

  PMID: 28539464 DERIVED

Related Links

• Corporate webpage

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; reparixin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr Pier Adelchi Ruffini, MD
• Organization: Dompé Farmaceutici SpA

info@dompe.it

+39 02 583831

Study Officials

• Lori J Goldstein, MD

  FASCOFox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2015
• First Posted: February 24, 2015
• Study Start: July 29, 2015
• Primary Completion: February 20, 2019
• Study Completion: March 23, 2020
• Last Updated: September 16, 2022
• Results First Posted: June 2, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (32); FR (8); IT (12); PL (6); ES (7); CZ (7); BE (5)