Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Fatigue

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Taxane

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.

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

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

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

Enrico Minnella, MD

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.

This is a phase 2, multinational, multicenter, randomized, double-blind, placebo-controlled study. It will evenly randomize 68 evaluable men and women adult patients with CRF in locally advanced or metastatic breast cancer who are candidates to start single-agent taxane chemotherapy (paclitaxel, nab-paclitaxel or docetaxel). CRF will be assessed at baseline on a scale from 0 - 10 (with 10 being most severe), enrolling any patient who report a score of 1 - 6. Recruitment will be competitive among the study sites, until the planned number of patients is randomized. Patients will be assigned (1:1) to receive either oral reparixin treatment (1200 mg t.i.d. - treatment group) or masked placebo t.i.d. (control group). Randomization will be stratified by site and according to the type of chemotherapy (paclitaxel vs docetaxel vs nab-paclitaxel). Sparse blood samples will be collected in the whole population for reparixin (and metabolites), docetaxel, nab-paclitaxel, paclitaxel PK analysis. Reparixin or placebo will be administered for 16 weeks or until disease progression, withdrawal of consent or unacceptable toxicity, whichever occurs first. Following the completion of the treatment, or after premature discontinuation during the double-blind phase the patients will be followed up for safety assessments for an additional 30 days after last study therapy administration and will be followed for progressive disease and survival until twelve months after last enrolled subject off treatment, or until trial is terminated for other reasons, whatever occurs first.

Number of Patients Sixty-eight (68) evaluable adult patients with CRF with locally advanced or metastatic breast cancer who are candidates to receive single-agent taxane chemotherapy will be included in the study. Assuming that 10% of subjects will not be evaluable for primary analysis, a total of approximately 76 subjects is expected to be enrolled.

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

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 2 Study to Assess Efficacy and Safety of Reparixin in Cancer Related Fatigue in Pts With Advanced / Metastatic Breast Cancer Undergoing Taxane-based Chemotherapy.

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.

The EQ-5D-5L consists of 2 pages: the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box of the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that describes the patient's health state.The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS is used as a quantitative measure of health outcome that reflect the patient's own judgment.

The PGI-S is designed to capture subject's perception of overall symptom severity at the time of completion on a 5-point categorical response scale: "Please choose the response below that best describes the severity of your fatigue over the past week" and is scored from 1 to 5, with 1 indicating "None", 2 "Mild", 3 "Moderate", 4 "Severe", 5 "Very Severe". The higher the score, the worse the outcome.

The PGI-C is designed to capture the subject's perception of change in their overall symptom severity from baseline until the time of completion. Change in severity is captured using a 5- point scale: "Please choose the response below that best describes the overall change in your fatigue since you started receiving the taxane-based chemotherapy" and is scored from 1 to 5, with 1 indicating "Much better", 2 "A little better", 3 "No change", 4 "A little worse", 5 "Much worse". The higher the score, the worse the outcome.

Proportion of patients delaying next dosing of chemotherapy due to chronic renal failure (CRF)

Proportion of patients discontinuing chemotherapy due to chronic renal failure (CRF)

ECOG PS is graded as follow:

0 Fully active, able to carry on all pre-disease performance without restriction

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5. Dead The higher the score, the worse the outcome.

ORR is defined as the proportion of patients with best overall response of CR or PR according to RECIST 1.1.

PFS is defined as the time from the date of randomization until the date of the first documented progression or death due to any cause. PFS will be assessed based on local investigator assessment per RECIST 1.1.

OS is defined as the time from date of first administration of study treatment until date of death due to any cause

Dompé Farmaceutici S.p.A

Blood and Lymph Conditions

Heart and Blood Diseases

Rare Diseases

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

Eligible patients will receive oral reparixin three times daily on a 4-week cycle for a core study period of 6 cycles (24 weeks). After cycle 6, patients may continue receiving reparixin once daily on a 4-week cycle if at least stable disease (SD) is met by IWG-MRT criteria until loss of response, disease progression, unacceptable toxicity, patient/physician withdrawal, or termination of study by sponsor.

reparixin at 1200mg TID three times per day.

reparixin

Mikaela Dougherty, MS

Marina Kremyanskaya

Marina Kremyanskaya, PhD, MD

Aaron Gerds, MD, MS

This is an open label, phase II study to assess the efficacy, safety, and tolerability of Reparixin in patients with DIPSS intermediate-2, or high-risk primary myelofibrosis (PMF), post essential thrombocythemia/polycythemia vera related MF (Post ET/PV MF) after prior treatment, and those who are ineligible or refuse treatment, with a Janus kinase inhibitor (JAKi). 26 patients will be enrolled. Eligible patients will receive oral reparixin three times daily on a 4-week cycle for a core study period of 6 cycles (24 weeks). After cycle 6, patients may continue receiving reparixin once daily on a 4-week cycle if at least stable disease (SD) is met by IWG-MRT criteria until loss of response, disease progression, unacceptable toxicity, patient/physician withdrawal, or termination of study by sponsor.

Reparixin in Patients With Myelofibrosis Myeloproliferative Neoplasms Research Consortium (MPN-RC 120)

Phase II Study of Reparixin in Patients With Myelofibrosis Myeloproliferative Neoplasms Research Consortium [MPN-RC 120]

To estimate the efficacy of reparixin treatment in DIPSS intermediate-2 or high-risk subjects with PMF, post PV-MF, or post ET-MF as assessed by IWG/ELN criteria. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission

Response by IWG/ELN criteria at the end of Cycle 6. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission

Response by IWG/ELN criteria at the end of Cycle 12. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission

Bone marrow fibrosis grade at the end of Cycle 6. Bone marrow fibrosis (MF) is graded as MF-0 to MF-3, with higher number indicating more disease.

Bone marrow fibrosis grade at the end of Cycle 12. Bone marrow fibrosis (MF) is graded as MF-0 to MF-3, with higher number indicating more disease.

To assess the safety of reparixin as measured by the adverse event profile of CTCAE v5.0.

Change in spleen volume by imaging after cycle 6 as compared to baseline spleen volume.

Change in spleen volume by imaging after cycle 12 as compared to baseline spleen volume.

Icahn School of Medicine at Mount Sinai

Associate Professor

Triple Negative Breast Neoplasms

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

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 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

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

paclitaxel

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

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

placebo

Lori J Goldstein, MD

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).

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.

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

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)

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.

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 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.

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.

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

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.

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.

A serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose

1. - results in death, (fatal)
2. - is life-threatening
3. - requires inpatient hospitalization or causes prolongation of existing hospitalization
4. - results in persistent or significant disability/incapacity,
5. - may have caused a congenital anomaly/birth defect, or
6. - requires intervention to prevent permanent impairment or damage.

PRA Health Sciences

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.

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+Reparixin (Group 1) - 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.

Paclitaxel+Placebo (Group 2) - Safety Population

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Belgium

United States

Czechia

Poland

Italy

France

Spain

Region of Enrollment

The Safety Population consisted of 121 patients who took at least one dose of study treatment

Dr Pier Adelchi Ruffini, MD

Paclitaxel+Reparixin (Group 1) - ITT Population

Paclitaxel+Placebo (Group 2)

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.

Progression Free Survival (PFS)

Overall Survival (OS)

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.

Objective Response Rate (ORR)

Median Progression-free Survival (mPFS)

Group 1 - Response Evaluable Population

Group 2 - Response-Evaluable Population

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.

Duration of Overall Response (DOR)

Unable to determine

Unknown/not done

Best Overall Response (BOR)

Overall

Grade 1 (mild)

Grade 2 (moderate)

Grade 3 (severe)

Grade 4 (Life-threatening or disabling)

Grade 5 (death)

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
To Assess Efficacy and Safety of Oral Reparixin in Patients With Fatigue and Locally Advanced / Metastatic Breast Cancer	NCT05212701	Fatigue Locally Advance...	Reparixin Placebo	18 Years -	Dompé Farmaceutici S.p.A
Reparixin in Patients With Myelofibrosis Myeloproliferative Neoplasms Research Consortium (MPN-RC 120)	NCT05835466	Myelofibrosis (... Post Essential ... Post Polycythem...	reparixin	18 Years -	Icahn School of Medicine at Mount Sinai
A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer	NCT02370238	Metastatic Brea...	paclitaxel Reparixin placebo	18 Years -	Dompé Farmaceutici S.p.A
A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer	NCT02370238	Metastatic Brea...	paclitaxel Reparixin placebo	18 Years -	Dompé Farmaceutici S.p.A
To Assess Efficacy and Safety of Oral Reparixin in Patients With Fatigue and Locally Advanced / Metastatic Breast Cancer	NCT05212701	Fatigue Locally Advance...	Reparixin Placebo	18 Years -	Dompé Farmaceutici S.p.A
To Assess Efficacy and Safety of Oral Reparixin in Patients With Fatigue and Locally Advanced / Metastatic Breast Cancer	NCT05212701	Fatigue Locally Advance...	Reparixin Placebo	18 Years -	Dompé Farmaceutici S.p.A
A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer	NCT02370238	Metastatic Brea...	paclitaxel Reparixin placebo	18 Years -	Dompé Farmaceutici S.p.A

Spots Global Cancer Trial Database for reparixin

Every month we try and update this database with for reparixin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for reparixin

Every month we try and update this database with for reparixin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for reparixin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.