To Assess Efficacy and Safety of Oral Reparixin in Patients With Fatigue and Locally Advanced / Metastatic Breast Cancer

NCT05212701 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: REP01212021-000382-32
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 20

Brief Summary

Primary objective:

• To assess the efficacy of reparixin compared to placebo in limiting CRF in adult patients with locally advanced or metastatic breast cancer undergoing single-agent taxane chemotherapy, using FACITFatigue scale. The secondary objectives are:
• To evaluate change in Quality of Life in the two treatment arms
• To assess the percentage of patients treated with reparixin compared to placebo delaying and discontinuing chemotherapy
• To assess Patient Global Impression of Severity (PGI-S) score and Patient Global Impression of Change (PGI-C) score associated with reparixin compared to placebo
• To assess the effect of reparixin compared to placebo on ECOG PS
• To assess the effects of reparixin vs placebo on Objective Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS) The safety objective is:
• To assess the safety and tolerability of reparixin in adult patients undergoing taxane-containing chemotherapy. The pharmacokinetic (PK) objective is:
• To define the PK profile of orally administered reparixin, its metabolites (DF2243Y, DF2188Y, ibuprofen) and concomitant antineoplastic agents (paclitaxel, or nab-paclitaxel or docetaxel) in adult patients with locally advanced or metastatic breast cancer.

Conditions

Fatigue; Locally Advanced or Metastatic Breast Cancer

Keywords

metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• Change from baseline in FACIT-F score

  The Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-fatigue) scale is a 13-item instrument designed to assess fatigue/ tiredness and its impact on daily activities and functioning in a number of chronic diseases. The instrument includes items such as tiredness, weakness, listlessness, lack of energy, and the impact of these feelings on daily functioning (e.g., sleeping, and social activities). The FACIT-fatigue scale is a 13-item patient-reported measure of fatigue where items are scored on a 0 - 4 response scale with anchors ranging from "Not at all" to "Very much so". To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52, where higher scores represent better functioning or less fatigue.

  week 16

Secondary Outcomes (10)

• Change from baseline in FACIT-F score

  weeks 4, 8 and 12

• EQ-5D-5L score

  day 1 of each 21- or 28-day cycle, off treatment visit (or withdrawal), which means up to 70 weeks

• Patient Global Impression of Severity (PGI-S) score

  day 1 of each 21- or 28-day cycle, off treatment visit (or withdrawal) which means up to 70 weeks

• Patient Global Impression of Change (PGI-C) score

  day 1 of each 21- or 28-day cycle except for cycle 1, off treatment visit (or withdrawal), which means up to 70 weeks

• Proportion of patients delaying next administration of chemotherapy due to CRF

  throughout the study, up to 70 weeks

Study Arms (2)

Reparixin

EXPERIMENTAL

Reparixin will be administered orally at the dose of 1200 mg (2 x 600 mg tablets) three times daily (total dose of 3600 mg/day) with no interruptions during each cycle.

Drug: Reparixin

Placebo

PLACEBO COMPARATOR

Masked placebo will be administered orally (2 tablets) three times daily with no interruptions during each cycle.

Drug: Placebo

Interventions

Reparixin DRUG

The oral tablets of the investigational product (IP) will be administered with water prior to the start of the anticancer treatment infusion on Day 1 Cycle 1 and then administered approximately every eight hours (± 2 h) with a glass of water (about 250 mL) and a light meal or snack (it is preferable that reparixin is taken with food).

Reparixin

Placebo DRUG

The oral tablets of masked placebo will be administered with water prior to the start of the anticancer treatment infusion on Day 1 Cycle 1 and then administered approximately every eight hours (± 2 h) with a glass of water (about 250 mL) and a light meal or snack

Placebo

Eligibility Criteria

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

You may qualify if:

• \. Provide written informed consent before the initiation of any study-specific procedures
• \. Male or female ≥18 years of age
• \. Pathologically documented locally advanced (not amenable to surgical resection) or metastatic HER2-negative breast cancer
• \. Candidate to receive cycle 1 of treatment with single-agent taxane-based chemotherapy (paclitaxel, nab-paclitaxel, docetaxel)
• \. CRF score from 1 to 6 on a numeric rating scale (NRS) from 0 to 10, where 0 = no fatigue, 10 = worst possible fatigue, during the previous 24 hours and lasting for a minimum of 4 days
• \. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
• \. Life expectancy of at least 6 months as estimated by the investigator
• \. Able to swallow and retain oral medication (intact tablet)
• \. 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 ≥ 11 g/dL; absolute neutrophil count ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L.
• Serum bilirubin ≤ upper limit of normal (ULN), except patients with Gilbert's syndrome.
• Serum Alanine aminotransferase (ALT), aspartate transaminase (AST) ≤ 1.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• prothrombin time (PT) or activated partial thromboplastin time (aPTT, PTT) ≤ULN

You may not qualify if:

• \. More than 1 prior systemic chemotherapy for advanced disease. Patients may have received hormone therapy and biological therapy (e.g. CDK4/6 inhibitors), either alone or in combination
• \. Malabsorption syndrome or disease significantly affecting gastrointestinal function including but not limited to gastrectomy or gastric outlet obstruction
• \. History or evidence of neurological or psychiatric disorder or any other concurrent medical condition or disease that, in the opinion of the investigator or Medical Monitor may influence understanding of study and informed consent procedures, would pose a risk to subject safety or would interfere with the study evaluation, procedures or completion
• \. Positive severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) antigenic test performed through nasal swab
• \. Treatment with any investigational agent within at least 28 days or 5 half-lives (whatever is shorter) prior to Visit 1, recovered from previous treatment toxicity to Grade1 or better
• \. Brain metastases that are untreated or symptomatic, or require any radiation, surgery, or continued steroid therapy to control symptoms from brain metastases
• \. Treatment with oral morphine greater than 60 mg a day or equivalent
• \. Other causes of fatigue, including, but not restricted to:
• untreated hypothyroidism
• pituitary disorder
• insomnia
• alcohol abuse
• uncontrolled pain as defined by pain intensity greater than 3 on a NRS (0-10)
• chronic \>G2 anemia
• uncontrolled cardiac disease or cardiovascular disorders

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (20)

Waverly Hematology

Cary, North Carolina, 27518, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Kliniken Essen-Mitte, Klinik für Senologie/ Interdisziplinäres Brustzentrum

Essen, 45136, Germany

Location

Praxis für Interdisziplinäre Onkologie & Hämatologie

Freiburg im Breisgau, 79110, Germany

Location

Mammazentrum Hamburg am Krankenhaus Jerusalem

Hamburg, 20357, Germany

Location

Klinikum Ernst von Bergmann, Frauenklinik

Potsdam, 14467, Germany

Location

IRCCS Oncologico Istituto Tumori Giovanni Paolo II

Bari, 70124, Italy

Location

Azienda Ospedaliero Universitaria di Bologna - Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

ASST-Spedali Civili di Brescia

Brescia, 25123, Italy

Location

E.O. Ospedali Galliera

Genova, 16128, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e La Cura dei Tumori SRL IRCCS

Meldola (FC), 47014, Italy

Location

IRCCS - Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Azienda Ospedaliera di Perugia, Ospedale Santa Maria della Misericordia

Perugia, 06132, Italy

Location

Azienda Ospedaliera Universitaria Pisana

Pisa, 56126, Italy

Location

"Azienda Unità Sanitaria Locale della Romagna Ospedale Infermi di Rimini"

Rimini, 47923, Italy

Location

Istituti Fisioterapici Ospitalieri- IFO - Istituto Regina Elena

Roma, 00144, Italy

Location

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Roma, 00168, Italy

Location

"Azienda Ospedaliero Universitaria Sant'Andrea "

Roma, 00189, Italy

Location

Ospedale Giuseppe Mazzini di Teramo

Teramo, 64100, Italy

Location

A.O. "Pia Fondazione Cardinale Panico"

Tricase, 73039, Italy

Location

MeSH Terms

Conditions

Fatigue; Breast Neoplasms

Interventions

reparixin

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Enrico Minnella, MD

  Dompé Farmaceutici S.p.A

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: December 29, 2021
• First Posted: January 28, 2022
• Study Start: April 19, 2022
• Primary Completion: June 1, 2023
• Study Completion: July 1, 2024
• Last Updated: April 30, 2024

Record last verified: 2024-04

Locations

US (2); DE (4); IT (14)