Metastatic Breast CancerPhase 1NCT02001974
Pilot Study to Evaluate Reparixin With Weekly Paclitaxel in Patients With HER 2 Negative Metastatic Breast Cancer (MBC)
A Phase 1 study testing Paclitaxel+Reparixin in people with Metastatic Breast Cancer, run by Dompé Farmaceutici S.p.A at 5 sites in United States.
Trial summary
This is a phase I study to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER 2 (Human epidermal growth factor receptor-2) negative metastatic breast cancer patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Paclitaxel+Reparixin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 5 sitesUnited States
- Study dates
- 27 Feb 2012to 15 Jan 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female aged ≥ 18 years.
- Patients with histologic or cytologic diagnosis of breast cancer with evidence of metastatic disease with documented HER-2 negative status and eligible for treatment with paclitaxel.
- Patients with at least one baseline measurable lesion according to RECIST version 1.1 criteria.
- Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0-1.
- An electrocardiogram (ECG) with no clinically significant abnormalities indicative of myocardial ischemia.
- Ongoing toxicity associated with prior anticancer therapy ≤ grade 1 Common Terminology Criteria for Adverse Events (CTCAE version 4.03) with the exception of alopecia.
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- Maximum of three prior chemotherapy lines for advanced breast cancer (not including neo/adjuvant chemotherapy). If prior treatment with paclitaxel, PD must have occurred > 12 months from the end of previous adjuvant treatment or for previous metastatic treatment no PD must have occurred during treatment or within 3 months of the end of treatment
- 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 following written informed consent.
- Adequate organ function (defined by the following parameters):
- Serum creatinine < 140 µmol/L 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).
- Serum ALT, AST ≤ 2.5 x UNL but ≤ 5.0 x UNL in case of liver metastases; ALP ≤ UNL but ≤ 1.5 x ULN in case of liver metastases; albumin within normal limits. If ALP is greater than 1.5 x UNL (in the presence of liver metastases) the liver isoenzyme fraction will be measured. Liver isoenzyme fraction (absolute value) must be ≤ 1.5 x UNL.
- No known hepatitis B virus (not due to immunization), hepatitis C virus, human immunodeficiency virus Ι and -ΙΙ positive status.
Who cannot join
- Male.
- Pregnancy or lactation or unwillingness to use adequate method of birth control.
- HER-2 positive disease status.
- Less than four weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than two weeks since last hormone or immunotherapy or signal transduction therapy.
- Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.
- Active or uncontrolled infection.
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- Malabsorption syndrome, disease significantly affecting gastrointestinal function.
- Hypersensitivity to:
- paclitaxel
- ibuprofen or to more than one non-steroidal anti-inflammatory drug.
- medications belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.
- Presence of brain metastases (this does not include primary brain tumors) or leptomeningeal disease.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Michigan; 1500 East Medical Center Drive
Ann Arbor, Michigan, 48109-5000
University of Kansas Medical Center; 4350 Shawnee Mission Parkway
Fairway, Kansas, 66205
Thomas Jefferson University Hospital; 1025 Walnut Street
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center; 333 Cottman Avenue
Philadelphia, Pennsylvania, 19111
Pinnacle Oncology Hematology; 9055 East Del Camino
Scottsdale, Arizona, 85258
About this study
Official title: Phase Ib Pilot Study to Evaluate Reparixin in Combination With Chemotherapy With Weekly Paclitaxel in Patients With HER 2 Negative Metastatic Breast Cancer (MBC)
This is a phase I study to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER 2 (Human epidermal growth factor receptor-2) negative metastatic breast cancer patients.
The primary objective of this study was to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER-2 negative MBC patients.
Read more
The secondary objectives were to:
- Evaluate the effects of orally administered reparixin on cancer stem cell (CSC) markers, the tumoral microenvironment and markers of cytokine inflammation;
- Evaluate peripheral blood samples for enumeration of circulating tumor cells (CTCs), molecular characterization as CSCs and perform epithelial-mesenchymal transition (EMT) biomarker profiling;
- Assess disease response for indication of efficacy.
Read the detailed description
The CSC (Cancer stem cell) concept has important implications for understanding carcinogenesis as well as for the development of cancer therapeutics. According to this concept, tumors are initiated and maintained by a cellular subcomponent that displays stem cell properties. These properties include self-renewal, which drives tumorigenesis, and differentiation (albeit aberrant), which contributes to tumor cellular heterogeneity. The existence of CSCs has been described in a variety of hematologic and solid tumors including those of the breast, brain, colon, pancreas, lung, liver, and head and neck. In addition to driving tumorigenesis, CSCs may contribute to tumor metastasis as well as to tumor recurrence after treatment.
One of the therapeutic strategies being pursued to target CSCs involves inhibition of self renewal or survival pathways in these cells. These pathways include NOTCH (Notch signaling pathway), Hedgehog, and WNT (Wnt signaling pathway). Such strategies may be limited by the role of these pathways in normal stem cell function, which could result in systemic toxicities from pathway inhibition. In addition to intrinsic pathways regulating stem cell functions, normal and malignant stem cells are regulated by extrinsic signals generated in the microenvironment or CSC niche. In the breast, this niche is composed of immune cells, mesenchymal elements that include fibroblasts, endothelial cells, adipocytes, and extracellular matrix components. These components play an important role in normal breast development and carcinogenesis. If the cellular microenvironment plays an important role in the regulation of CSC growth and survival, then strategies aimed at interfering with these interactions represent a rational approach to target breast CSCs.
There are limited data on the impact of treatment tailoring based on CSCs detection. Gene profiling of CSCs could lead to identification of therapeutic targets on CSCs (e.g. hormone receptors, HER-2 [Human epidermal growth factor receptor-2] expression, EGFR [Epidermal growth factor receptor] expression), and could represent tumor biopsy in "real time". Several groups showed frequent discordance of HER-2 status between primary tumor and CSCs, and case reports showed clinical utility to use of trastuzumab-based therapy based on HER-2 CSCs status. Similarly, the hormonal status of CSCs could be different from that of the primary tumor, which could lead to increase the number of patients suitable for endocrine therapy, but also could explain why endocrine therapy fails in a subset of hormone receptor-positive patients. The study provided the in vivo demonstration that CXCR-1 (Chemokine receptor 1) targeting with specific blocking antibodies or reparixin is associated with reduced systemic metastases. The experimental data provides another therapeutic target in metastatic disease and warrants a pilot study investigation in humans to further explore effects of reparixin on breast CSCs and the tumoral microenvironment.
Reparixin seems to be a good candidate for use in breast cancer patients because of its very acceptable toxicity profile shown in the Phase I and II clinical trials conducted so far, along with its observed activity in vitro against breast cancer cell lines and in vivo in tumor xenografts in mice. It potentially addresses another therapeutic target in metastatic disease. The current pilot study thus aims at exploring the safety and PK profile of orally administered reparixin in HER-2 negative metastatic breast cancer patients and its effects on breast CSC markers.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Paclitaxel+Reparixin
- Keywords
- HER 2 negative, metastatic breast cancer, Cancer Stem Cells
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paclitaxel+ReparixinDrug
Also called PAC + REP
Association of Paclitaxel at fixed dosage with three increasing dosage of Reparixin
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients) Receives: Drug: Paclitaxel+Reparixin |
| Group 2 | Experimental | Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients) Receives: Drug: Paclitaxel+Reparixin |
| Group 3 | Experimental | Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients). Receives: Drug: Paclitaxel+Reparixin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-Emergent Adverse Events (TEAEs)
Monitoring of AEs throughout the study till the end/off-treatment visit.
Measured: Up to 28 days following the last dose of study drug (up to 24 months).
Plasma DF1681Y Concentrations by Time Point
Plasma DF 1681Y concentrations are reported by time point for the PK Population. The CSR also presents:
- plots of mean plasma PK concentrations versus time for DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population;
- plots of individual plasma PK concentrations versus time for DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; and
- a plot of reparixin versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
Plasma Unbound DF1681Y Concentrations by Time Point
Plasma unbound DF 1681Y concentrations by time point for the PK Population are reported. CSR also presents:
- plots of mean plasma PK concentrations versus time for unbound DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; and
- plots of individual plasma PK concentrations versus time for unbound DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population.
Measured: Days -3 (1, 2 hours), 1 (1, 2 hours), 8 (1, 2 hours), and 21 (1, 2 hours) of cycle 1.
Plasma DF2243Y Concentrations by Time Point
DF2243Y, DF2188Y, methanesulfonamide and ibuprofen are the metabolites detected in human plasma and urine, with DF2243Y being the major metabolite. Plasma DF 2243Y concentrations by time point for the PK Population are reported. CSR also presents:
- plots of mean plasma PK concentrations versus time for DF 2243Y on Days -3, 1, 8 and 21, respectively (linear and semi-logarithmic) for the PK Population;
- plots of individual plasma PK concentrations versus time for DF 2243Y on Days -3, 1, 8 and 21 (linear and semi-logarithmic) for the PK Population;
- a plot of DF 2243Y versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
Plasma DF2188Y Concentrations by Time Point
DF2243Y, DF2188Y, methanesulfonamide and ibuprofen are the metabolites detected in human plasma and urine, with DF2243Y being the major metabolite. Plasma DF 2188Y concentrations by time point for the PK Population are reported. CSR also presents:
- a plot of mean plasma PK concentrations versus time for DF 2188Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population;
- plots of individual plasma PK concentrations versus time for DF 2188Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population;
- a plot of DF 2881Y versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
Plasma Ibuprofen Concentrations by Time Point
DF2243Y, DF2188Y, methanesulfonamide and ibuprofen are the metabolites detected in human plasma and urine, with DF2243Y being the major metabolite.
Plasma ibuprofen concentrations are reported by time point for the PK Population. CSR describes also:
- a plot of mean plasma PK concentrations versus time for ibuprofen on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population;
- plots of individual plasma PK concentrations versus time for ibuprofen on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population;
- a plot of ibuprofen versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
Plasma Paclitaxel Concentrations by Time Point
Plasma paclitaxel concentrations are reported by time point for the PK Population. CSR describes also:
- A plot of mean plasma PK concentrations versus time for paclitaxel on Days 1 and 8 respectively (linear and semi-logarithmic) for the PK Population;
- plots of individual plasma PK concentrations versus time for paclitaxel on Days 1 and 8 respectively (linear and semi-logarithmic) for the PK Population;
- a plot of paclitaxel versus time on Day 1 and Day 8 on a linear (upper) or semi-log (lower) axis.
Measured: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours) and 8 (0, 0.5, 1, 2, 4, 8, 24 hours) of cycle 1.
C0 and Cmax for DF1681Y
PK parameters were calculated for cycle 1 only.
Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
C0 and Cmax for DF2243Y
PK parameters were calculated for cycle 1 only.
Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
C0 and Cmax for DF2188Y
PK parameters were calculated for cycle 1 only.
Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Measured: Days -3 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours), 1 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours), 8 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours) and 21 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours)
C0 and Cmax for Ibuprofen
PK parameters were calculated for cycle 1 only.
Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
Cmax for Paclitaxel
PK parameters were calculated for cycle 1 only.
Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Measured: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours)
Tmax and t1/2 for DF1681Y
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation.
t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
Tmax and t1/2 for DF2243Y
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation.
t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
Tmax and t1/2 for DF2188Y
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation.
t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
Tmax and t1/2 for Ibuprofen
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation.
t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
Tmax and t1/2 for Paclitaxel
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation.
t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Measured: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours)
AUC0-8 for DF1681Y
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
AUC0-8 for DF2243Y
PK parameters were calculated for cycle 1 only. AUC0-8 is The area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
AUC0-8 for DF2188Y
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
AUC0-8 for Ibuprofen
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
AUC0-8 for Paclitaxel
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Measured: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours).
Rac0-8 for DF1681Y
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Measured: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
Rac0-8 for DF2243Y
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Measured: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
Rac0-8 for DF2188Y
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Measured: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
Rac0-8 for Ibuprofen
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Measured: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
Rac0-24 for Paclitaxel
PK parameters were calculated for cycle 1 only. Rac AUC0-24 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-24.
Measured: Day 8 (0, 0.5, 1, 2, 4, 8, 24 hours)
Secondary outcomes (5)
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Complete Response/Remission(CR): Disappearance of all target lesions. Partial Response/Remission (PR): At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD.
Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started.
Progression of Disease (PD): At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Measured: At tumor assessments 1-11 and off-treatment visit
Best Overall Response (BOR)
The best overall response (BOR) was defined as the number of patients reaching complete remission (CR), partial remission (PR) or stable disease (SD) according to RECIST criteria version 1.1
Measured: After 24 weeks
Clinical Benefit Rate (CBR)
The clinical benefit rate (CBR) was defined as the percentage of patients reaching CR, PR or SD according to RECIST criteria version 1.1
Measured: After 24 weeks
6-month Progression-free Survival Rate
The 6-month progression-free survival rate (%) was defined as the percentage of patients with no mortality and at least 24-week duration of CR, PR or SD according to RECIST criteria version 1.1
Measured: After 24 weeks
Median Time to Tumor Progression in Days (TTP)
The median time to tumor progression in days (TTP) was defined as the time from the date of the first administration of study drug to the date of the first documentation of progressive disease
Measured: After 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2013 (estimated)
- Study start27 Feb 2012
- Primary completion25 Jun 2014
- Study completion15 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dompé Farmaceutici S.p.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Anne Schott, MD, Principal investigator, University of MichiganLori Goldstein, MD, Principal investigator, Fox Chase Cancer CenterRaymond Perez, MD, Principal investigator, University of Kansas Medical CenterTiffany Avery, MD, Principal investigator, Thomas Jefferson UniversityGiraldo Kato, MD, Principal investigator, Pinnacle Oncology Hematology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02001974
- Sponsor's protocol ID
- REP0111
- Status last verified
- Sep 2021
- First submitted
- 15 Nov 2013
- Last updated
- 27 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Pilot Study to Evaluate Reparixin in Combination With Chemotherapy With Weekly Paclitaxel in Patients With HER 2 Negative Metastatic Breast Cancer (MBC)
- ClinicalTrials.gov ID
- NCT02001974
- Acronym / sponsor ID
- REP0111
- Conditions
- Metastatic Breast Cancer
- Keywords
- HER 2 negative, metastatic breast cancer, Cancer Stem Cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Dompé Farmaceutici S.p.AIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 27 Feb 2012 (actual)
- Primary completion
- 25 Jun 2014 (actual)
- Study completion
- 15 Jan 2015 (actual)
- First posted
- 5 Dec 2013 (estimated)
- Results
- Posted 19 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I study to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER 2 (Human epidermal growth factor receptor-2) negative metastatic breast cancer patients.
The primary objective of this study was to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER-2 negative MBC patients.
The secondary objectives were to:
- Evaluate the effects of orally administered reparixin on cancer stem cell (CSC) markers, the tumoral microenvironment and markers of cytokine inflammation;
- Evaluate peripheral blood samples for enumeration of circulating tumor cells (CTCs), molecular characterization as CSCs and perform epithelial-mesenchymal transition (EMT) biomarker profiling;
- Assess disease response for indication of efficacy.
Detailed description
The CSC (Cancer stem cell) concept has important implications for understanding carcinogenesis as well as for the development of cancer therapeutics. According to this concept, tumors are initiated and maintained by a cellular subcomponent that displays stem cell properties. These properties include self-renewal, which drives tumorigenesis, and differentiation (albeit aberrant), which contributes to tumor cellular heterogeneity. The existence of CSCs has been described in a variety of hematologic and solid tumors including those of the breast, brain, colon, pancreas, lung, liver, and head and neck. In addition to driving tumorigenesis, CSCs may contribute to tumor metastasis as well as to tumor recurrence after treatment.
One of the therapeutic strategies being pursued to target CSCs involves inhibition of self renewal or survival pathways in these cells. These pathways include NOTCH (Notch signaling pathway), Hedgehog, and WNT (Wnt signaling pathway). Such strategies may be limited by the role of these pathways in normal stem cell function, which could result in systemic toxicities from pathway inhibition. In addition to intrinsic pathways regulating stem cell functions, normal and malignant stem cells are regulated by extrinsic signals generated in the microenvironment or CSC niche. In the breast, this niche is composed of immune cells, mesenchymal elements that include fibroblasts, endothelial cells, adipocytes, and extracellular matrix components. These components play an important role in normal breast development and carcinogenesis. If the cellular microenvironment plays an important role in the regulation of CSC growth and survival, then strategies aimed at interfering with these interactions represent a rational approach to target breast CSCs.
There are limited data on the impact of treatment tailoring based on CSCs detection. Gene profiling of CSCs could lead to identification of therapeutic targets on CSCs (e.g. hormone receptors, HER-2 [Human epidermal growth factor receptor-2] expression, EGFR [Epidermal growth factor receptor] expression), and could represent tumor biopsy in "real time". Several groups showed frequent discordance of HER-2 status between primary tumor and CSCs, and case reports showed clinical utility to use of trastuzumab-based therapy based on HER-2 CSCs status. Similarly, the hormonal status of CSCs could be different from that of the primary tumor, which could lead to increase the number of patients suitable for endocrine therapy, but also could explain why endocrine therapy fails in a subset of hormone receptor-positive patients. The study provided the in vivo demonstration that CXCR-1 (Chemokine receptor 1) targeting with specific blocking antibodies or reparixin is associated with reduced systemic metastases. The experimental data provides another therapeutic target in metastatic disease and warrants a pilot study investigation in humans to further explore effects of reparixin on breast CSCs and the tumoral microenvironment.
Reparixin seems to be a good candidate for use in breast cancer patients because of its very acceptable toxicity profile shown in the Phase I and II clinical trials conducted so far, along with its observed activity in vitro against breast cancer cell lines and in vivo in tumor xenografts in mice. It potentially addresses another therapeutic target in metastatic disease. The current pilot study thus aims at exploring the safety and PK profile of orally administered reparixin in HER-2 negative metastatic breast cancer patients and its effects on breast CSC markers.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Paclitaxel+ReparixinPaclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients) |
| Group 2 | Experimental | Drug: Paclitaxel+ReparixinPaclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients) |
| Group 3 | Experimental | Drug: Paclitaxel+ReparixinPaclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Female aged ≥ 18 years.
- Patients with histologic or cytologic diagnosis of breast cancer with evidence of metastatic disease with documented HER-2 negative status and eligible for treatment with paclitaxel.
- Patients with at least one baseline measurable lesion according to RECIST version 1.1 criteria.
- Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0-1.
- An electrocardiogram (ECG) with no clinically significant abnormalities indicative of myocardial ischemia.
Key exclusion criteria (12 listed)
- Male.
- Pregnancy or lactation or unwillingness to use adequate method of birth control.
- HER-2 positive disease status.
- Less than four weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than two weeks since last hormone or immunotherapy or signal transduction therapy.
- Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Paclitaxel+ReparixinAlso: PAC + REPAssociation of Paclitaxel at fixed dosage with three increasing dosage of Reparixin | Drug | Group 1, Group 2, Group 3 |
Primary outcome
Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to 28 days following the last dose of study drug (up to 24 months).
Monitoring of AEs throughout the study till the end/off-treatment visit.
Plasma DF1681Y Concentrations by Time Point
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
Plasma DF 1681Y concentrations are reported by time point for the PK Population. The CSR also presents: * plots of mean plasma PK concentrations versus time for DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; and * a plot of reparixin versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Plasma Unbound DF1681Y Concentrations by Time Point
Time frame: Days -3 (1, 2 hours), 1 (1, 2 hours), 8 (1, 2 hours), and 21 (1, 2 hours) of cycle 1.
Plasma unbound DF 1681Y concentrations by time point for the PK Population are reported. CSR also presents: * plots of mean plasma PK concentrations versus time for unbound DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; and * plots of individual plasma PK concentrations versus time for unbound DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population.
Plasma DF2243Y Concentrations by Time Point
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
DF2243Y, DF2188Y, methanesulfonamide and ibuprofen are the metabolites detected in human plasma and urine, with DF2243Y being the major metabolite. Plasma DF 2243Y concentrations by time point for the PK Population are reported. CSR also presents: * plots of mean plasma PK concentrations versus time for DF 2243Y on Days -3, 1, 8 and 21, respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for DF 2243Y on Days -3, 1, 8 and 21 (linear and semi-logarithmic) for the PK Population; * a plot of DF 2243Y versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Plasma DF2188Y Concentrations by Time Point
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
DF2243Y, DF2188Y, methanesulfonamide and ibuprofen are the metabolites detected in human plasma and urine, with DF2243Y being the major metabolite. Plasma DF 2188Y concentrations by time point for the PK Population are reported. CSR also presents: * a plot of mean plasma PK concentrations versus time for DF 2188Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for DF 2188Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * a plot of DF 2881Y versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Plasma Ibuprofen Concentrations by Time Point
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
DF2243Y, DF2188Y, methanesulfonamide and ibuprofen are the metabolites detected in human plasma and urine, with DF2243Y being the major metabolite. Plasma ibuprofen concentrations are reported by time point for the PK Population. CSR describes also: * a plot of mean plasma PK concentrations versus time for ibuprofen on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for ibuprofen on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * a plot of ibuprofen versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Plasma Paclitaxel Concentrations by Time Point
Time frame: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours) and 8 (0, 0.5, 1, 2, 4, 8, 24 hours) of cycle 1.
Plasma paclitaxel concentrations are reported by time point for the PK Population. CSR describes also: * A plot of mean plasma PK concentrations versus time for paclitaxel on Days 1 and 8 respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for paclitaxel on Days 1 and 8 respectively (linear and semi-logarithmic) for the PK Population; * a plot of paclitaxel versus time on Day 1 and Day 8 on a linear (upper) or semi-log (lower) axis.
C0 and Cmax for DF1681Y
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
C0 and Cmax for DF2243Y
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
C0 and Cmax for DF2188Y
Time frame: Days -3 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours), 1 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours), 8 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours) and 21 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours)
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
C0 and Cmax for Ibuprofen
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Cmax for Paclitaxel
Time frame: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours)
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Tmax and t1/2 for DF1681Y
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Tmax and t1/2 for DF2243Y
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Tmax and t1/2 for DF2188Y
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Tmax and t1/2 for Ibuprofen
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Tmax and t1/2 for Paclitaxel
Time frame: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours)
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
AUC0-8 for DF1681Y
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
AUC0-8 for DF2243Y
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
PK parameters were calculated for cycle 1 only. AUC0-8 is The area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
AUC0-8 for DF2188Y
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
AUC0-8 for Ibuprofen
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
AUC0-8 for Paclitaxel
Time frame: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours).
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Rac0-8 for DF1681Y
Time frame: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Rac0-8 for DF2243Y
Time frame: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Rac0-8 for DF2188Y
Time frame: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Rac0-8 for Ibuprofen
Time frame: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Rac0-24 for Paclitaxel
Time frame: Day 8 (0, 0.5, 1, 2, 4, 8, 24 hours)
PK parameters were calculated for cycle 1 only. Rac AUC0-24 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-24.
5 secondary outcomes
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Time frame: At tumor assessments 1-11 and off-treatment visit
Best Overall Response (BOR)
Time frame: After 24 weeks
Clinical Benefit Rate (CBR)
Time frame: After 24 weeks
6-month Progression-free Survival Rate
Time frame: After 24 weeks
Median Time to Tumor Progression in Days (TTP)
Time frame: After 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne Schott, MD principal investigator
University of Michigan
Lori Goldstein, MD principal investigator
Fox Chase Cancer Center
Raymond Perez, MD principal investigator
University of Kansas Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Paclitaxel+Reparixin in people with Metastatic Breast Cancer, run by Dompé Farmaceutici S.p.A at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-Emergent Adverse Events (TEAEs) (time frame: Up to 28 days following the last dose of study drug (up to 24 months).). The study lists 27 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2021.