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

NCT ID: NCT02370238

Last Updated: 2022-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 194 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-29
• Study Completion Date: 2020-03-23

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).

Detailed Description

The study is a two arm, phase 2 study to evaluate the efficacy of the combination of paclitaxel and reparixin compared to paclitaxel and placebo in metastatic TNBC patients.

In the study two groups There were two groups:

Group 1: paclitaxel 80 mg/m2 intravenous (i.v.) (Days 1, 8, and 15 of 28-day cycle) + reparixin oral tablets 1200 mg three times a day (t.i.d.) continuing from Day 1 to Day 21.

Group 2: paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + placebo oral tablets 1200 mg t.i.d. continuing from Day 1 to Day 21.

Study drug (reparixin/placebo) was administered with water prior to the start of the i.v. paclitaxel infusion on Cycle 1, Day 1 and then administered approximately every eight hours (six to ten hours) for 21 consecutive days during each cycle with seven days off-treatment between each cycle. It was preferable that reparixin was taken with food. However, if the patient was unable to eat, study drug was allowed to be administered. When in combination with paclitaxel (Day 1, 8 and 15 of each cycle), reparixin or placebo was administered every approximately eight hours with about 250 mL water and a light meal or snack. Paclitaxel was administered in combination with study drug (reparixin/placebo) as an i.v. infusion on Days 1, 8 and 15 of each 28-day cycle.

On Cycle 1, Day 1, paclitaxel was administered at the clinic after the administration of study drug (reparixin/placebo). From that point forward, study drug (reparixin/placebo) was self-administered t.i.d. for 21 days. Combination treatment (three weeks on and one week off) continued until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.

The next clinic visits were on Days 8 and 15 when a paclitaxel infusion was administered to the patient. The patients returned to the clinic again on Day 29/Day 1 of the next cycle.

Tumor response and/or progression assessments were performed and documented every eight weeks according to RECIST criteria version 1.1. Metastatic tissue samples were analyzed for evaluation of CD24-CD44+ and aldehyde dehydrogenase positive (ALDH+) CSCs.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

paclitaxel

Intervention Type: DRUG

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

Reparixin

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

paclitaxel

Intervention Type: DRUG

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

placebo

Intervention Type: DRUG

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

Interventions

paclitaxel

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

Intervention Type: DRUG

Reparixin

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

Intervention Type: DRUG

placebo

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

Intervention Type: DRUG

Other Intervention Names

REP

Eligibility Criteria

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.

3. 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

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

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

6. Life expectancy of at least three months.

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

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

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

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

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

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

4. 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.

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

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

12. 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:

1. paclitaxel

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

Dompé Farmaceutici S.p.A

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lori J Goldstein, MD

Role: PRINCIPAL_INVESTIGATOR

FASCOFox Chase Cancer Center

Locations

Southern Cancer Center

Mobile, Alabama, United States

CBCC Global Research a Comprehensive Blood and Cancer Center

Bakersfield, California, United States

Florida Cancer Specialists

Daytona Beach, Florida, United States

Florida Cancer Specialists

West Palm Beach, Florida, United States

Atlanta Cancer Care

Alpharetta, Georgia, United States

Northside Hospital, Inc.-Georgia Cancer Specialists

Athens, Georgia, United States

Atlanta Cancer Care

Atlanta, Georgia, United States

Northside Hospital, Inc.

Atlanta, Georgia, United States

Northside Hospital, Inc.-Georgia Cancer Specialists

Canton, Georgia, United States

Atlanta Cancer Care

Conyers, Georgia, United States

Atlanta Cancer Care

Cumming, Georgia, United States

Atlanta Cancer Care

Decatur, Georgia, United States

Northside Hospital, Inc.-Georgia Cancer Specialists

Decatur, Georgia, United States

Atlanta Cancer Care

Jonesboro, Georgia, United States

Northside Hospital, Inc.-Georgia Cancer Specialists

Macon, Georgia, United States

Northside Hospital, Inc.-Georgia Cancer Specialists

Marietta, Georgia, United States

Southeastern Regional Medical Center

Newnan, Georgia, United States

Northside Hospital, Inc.-Georgia Cancer Specialists

Sandy Springs, Georgia, United States

Swedish Covenant

Chicago, Illinois, United States

Mid Illinois Hematology & Oncology Associates, Ltd.

Normal, Illinois, United States

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Summit Medical Group

Morristown, New Jersey, United States

Regional Cancer Care Associates

Sparta, New Jersey, United States

Waverly Hematology Oncology

Cary, North Carolina, United States

Hematology and Oncology Associates of Northeast PA

Dunmore, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Tennessee Oncology PLLC

Chattanooga, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

The Methodist Hospital

Houston, Texas, United States

Overlake Medical Center

Bellevue, Washington, United States

Fox Valley Hematology and Oncology, SC

Appleton, Wisconsin, United States

Algemeen Ziekenhuis Klina

Brasschaat, , Belgium

Cliniques Universitaires Saint- LUC UCL

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

CHU Ambroise Paré

Mons, , Belgium

AZ St Elisabeth

Namur, , Belgium

Masaryk Memorial Cancer Institute

Brno, , Czechia

Nemocnice Horovice a.s.

Hořovice, , Czechia

Fakultni nemocnice Hradec Králové

Hradec Králové, , Czechia

Fakultní nemocnice Královské Vinohrady

Prague, , Czechia

Onkologická klinika VFN a 1.LF UK

Prague, , Czechia

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

Prague, , Czechia

Krajská nemocnice T.Bati, a. s.

Zlín, , Czechia

Centre Paul Papin

Angers, , France

Centre François Baclesse

Caen, , France

Centre hospitalier de Saint-Brieuc, Yves Le Foll

La Roche-sur-Yon, , France

Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren

Limoges, , France

Institut Paoli Calmettes

Marseille, , France

Centre Antoine Lacassagne

Nice, , France

Hôpital Européen Georges Pompidou

Paris, , France

Medicale Centre René Gauducheau

Saint-Herblain, , France

Ospedale "Di Summa-Perrino"

Brindisi, , Italy

Azienda Ospedaliero-Universitaria

Cagliari, , Italy

Azienda Ospedaliero - Universitaria, Policlinico Vittorio Emanuele

Catania, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Ospedale dell'Angelo

Mestre, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Azienda Ospedaliera, Ospedale San Carlo Borromeo

Milan, , Italy

Fondazione IRCCS Policlinico S. Matteo

Pavia, , Italy

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, , Italy

Nuovo Ospedale

Prato, , Italy

Azienda Opspedaliero Universitaria Santa Maria della Misericordia

Udine, , Italy

Ospedale SS Giovanni e Paolo

Venezia, , Italy

Bialostockie Centrum Onkologii im. Marii Sklodowskiej - Curie

Bialystok, , Poland

Wojewódzkie Centrum Onkologii

Gdansk, , Poland

Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli

Lublin, , Poland

Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu

Poznan, , Poland

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

Rzeszów, , Poland

Magodent Sp. z o. o.

Warsaw, , Poland

Centro Oncológico Regional de Galicia, Servicio de Oncologia Medica

A Coruña, Galicia, Spain

Complejo Hospitalario Universitario La Coruña

A Coruña, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

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

Madrid, , Spain

C. Hospital Xeral-Cies

Vigo, , Spain

Countries

United States; Belgium; Czechia; France; Italy; Poland; Spain

References

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.

Reference Type: DERIVED

PMID: 28539464 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.dompe.com

Corporate webpage

Other Identifiers

2014-004796-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

REP0114

Identifier Type: -

Identifier Source: org_study_id