Pilot Study to Evaluate Safety & Biological Effects of Orally Administered Reparixin in Early Breast Cancer
Sponsor
Dompé Farmaceutici S.p.A (Industry)
Overall Status
Terminated
CT.gov ID
NCT01861054
Collaborator
(none)
20
9
1
36.9
2.2
0.1
Study Details
Study Description
Brief Summary
This is a pilot "window of opportunity" clinical study in patients with operable breast cancer investigating use of reparixin as single agent in the time period between clinical diagnosis and surgery.
The primary objectives of this study were:
1- to evaluate the effects of orally administered reparixin on CSCs in the primary tumor and the tumoral microenvironment in an early breast cancer population:
-
CSC were measured in tissue samples by techniques that could include: ALDEFLUOR assay and assessment of CD44/CD24 by flow cytometry, or examination of RNA transcripts by RT-PCR, aldehyde dehydrogenase-1, CD44/CD24 and epithelial mesenchymal transition markers (Snail, Twist, Notch) by immunohistochemistry (IHC). CSC were defined as ALDEFLUOR positive (ALDH-1+) and/or CD44 high/CD24 low by flow cytometry or RT-PCR and IHC and by the detection of ALDH-1+ cells with or without epithelial mesenchymal transition (EMT) transcription factor in IHC assays.
-
Serine-threonine protein kinase (AKT), focal adhesion kinase (FAK), phosphatase and tensin homolog (PTEN) and chemokine receptor-1 (CXCR1) levels were measured in tissue samples by IHC.
-
Measurement of markers of inflammation (interleukin-1beta [IL-1β], interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor-alpha [TNF-α], granulocyte macrophage colony stimulating factor [GM-CSF], vascular endothelial growth factor [VEGF], basic fibroblast growth factor [b-FGF] and high-sensitivity C-reactive protein [hsCRP]) in plasma, leukocyte subsets (enumerate T subsets, B, and natural killer/natural killer T [NK/NKT] cells) and study polymorphonuclear leukocyte [PMN] biology in peripheral blood samples. D. Measurement of markers of angiogenesis (CD31 staining), tumor-infiltrating leukocytes (CD4, CD8, NK and macrophages), autophagy (P62 and LC3 by IHC), EpCAM and EMT markers (CD326, CD45, Twist1, SNAIL1, SLUG, ZEB1, FOXC2, TG2, Akt2, P13k and CK19 by RT-PCR) and tissue cellularity (residual disease characterization in tumor bed) in tumor tissue samples.
- To evaluate the safety of oral reparixin administered three times daily (t.i.d.) for 21 consecutive days.
The secondary objective was to define the pharmacokinetic (PK) profile of orally administered reparixin.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
According to the cancer stem cell (CSC) model, tumors are organized in a cellular hierarchy maintained by a subpopulation of cells displaying stem cell properties. These properties include self-renewal (which drives tumorigenesis) and differentiation (which generates the tumor bulk and contributes to cellular heterogeneity).
CSCs were first observed in hematological malignancies but have also been identified in solid tumors of breast, prostate, brain, colon and pancreas. CSCs are thought to be resistant to conventional chemotherapies and this may be why relapse occurs in many patients and this might explain the failure to develop therapies that are consistently able to eradicate solid tumors. Although currently available drugs can shrink metastatic tumors, these effects are usually transient and often do not appreciably extend the life of patients. One reason for the failure of these treatments is the acquisition of drug resistance by the cancer cells as they evolve; another possibility is that existing therapies fail to kill CSCs effectively. Existing therapies have been developed largely against the bulk population of tumor cells because they are often identified by their ability to shrink tumors. Because most cancer cells have limited proliferative potential, an ability to shrink a tumor mainly reflects an ability to kill these cells. It seems that normal stem cells from various tissues tend to be more resistant to chemotherapeutics than mature cell types from the same tissues. The reasons for this are not clear, but may relate to high levels of expression of anti-apoptotic proteins or adenosine triphosphate-binding cassette transporters such as the multidrug resistance gene. If the same were true of CSCs, then one would predict that these cells would be more resistant to chemotherapeutics than tumor cells with limited proliferative potential. Even therapies that cause complete regression of tumors might spare enough CSCs to allow re-growth of the tumors. Therapies that are more specifically directed against CSCs might result in much more durable responses and even cures of metastatic tumors.
There are limited data on the impact of treatment tailoring based on CSC detection. Gene profiling of CSCs could lead to identification of therapeutic targets on CSCs (e.g. hormone receptors (HR), human epidermal growth factor receptor-2 [HER-2] expression, epidermal growth factor receptor [EGFR] 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 for the 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 HR positive (HR+) patients. More specifically, a recent observation from Ginestier et al. demonstrated that over expression of chemokine receptor 1 (CXCR-1) is associated with the aldehyde dehydrogenase positive (ALDH+) cells. In breast carcinomas, the ALDEFLUOR+ phenotype shows partial overlap with the CD44+CD24-Lin-CSC phenotype. Cellular hierarchies have been identified in a series of molecularly characterized breast cancer cell lines and it has been demonstrated that these lines contained ALDEFLUOR+ components that were both tumorigenic and metastatic in NOD/SCID mice. Furthermore, previous observations demonstrated that the addition of recombinant interleukin-8 (IL-8) increased the CSC population as well as increasing its propensity for invasion. Moreover, tissue damage induced by chemotherapeutic agents may induce IL-8 as part of the injury response. This suggests that strategies aimed at interfering with the IL 8/CXCR-1 axis may be able to target CSCs, increasing the efficacy of current therapies. This experimental data provides another therapeutic target in breast cancer.
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. A phase 1 study is currently underway to study the effects of reparixin in combination with paclitaxel in metastatic breast cancer.
This small pilot study aims at exploring the effects on breast CSC markers as well as the safety and PK profile of orally administered single agent reparixin in HER-2 negative (HER-2-) early breast cancer patients in the 3 weeks prior to surgery.
The study will be performed in the interval between disease diagnosis and planned surgery and may lead to a minimal delay in surgery. This is balanced by the potential benefits of the study by evaluating CSCs and their prognostic importance as well as obtaining information about the impact of reparixin therapy.
Study Design
Study Type:
Interventional
Actual Enrollment
:
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single Arm, Preoperative, Pilot Study to Evaluate the Safety and Biological Effects of Orally Administered Reparixin in Early Breast Cancer Patients Who Are Candidates for Surgery
Study Start Date
:
Feb 1, 2013
Actual Primary Completion Date
:
Mar 1, 2015
Actual Study Completion Date
:
Mar 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treated patients - Total Patients eligible will be treated with Reparixin as add-in monotherapy |
Drug: Reparixin
1000 mg Oral Reparixin t.i.d. for 21 consecutive days prior to surgery
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to Day 21 in Markers of Cancer Stem Cells (CSCs) in the Primary Tumor and the Tumoral Microenvironment (ALDH1,CD44/CD24) [At day 21]
CSCs were measured in tissue samples by the following techniques: ALDH-1 by ALDEFLUOR and by immunohistochemistry (IHC); CD44/CD24 by flow cytometry or examination of RNA transcripts by RT-PCR and by immunohistochemistry (IHC); epithelial mesenchymal markers (Snail, Twist, Notch) by immunohistochemistry (IHC).
- Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC [Day 21 (or last day of treatment)]
Pathway markers (AKT, FAK, PTEN and CXCR1) were measured in tissue samples at the pre-study (Day -14 to 0) and Day 21 (or within 24 hours of last dose). For the evaluation of the stain extent, the following semi-quantitative score method (0 to 4) was used: 0, no positive cells; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%. Hence for this scale, the higher the values, the worse is the outcome. For the evaluation of the stain intensity, the following score method (0 to 3) was used: 0, negative; 1, weak; 2, moderate, 3; strong. Also for this scale, the higher the score, the worse the outcome. Serine-threonine protein kinase (AKT, also known as protein kinase B, PKB) Focal adhesion kinase (FAK) Chemokine receptor-1 (CXCR1)
- Change From Baseline to Day 21 in Markers of Inflammation [At Day 21]
Markers of inflammation (IL-1β, IL-6, IL-8, TNF-α, GM-CSF, VEGF, and b-FGF) were measured in plasma from peripheral blood. IL = interleukins TNF-α = tumor necrosis factor-alpha GM-CSF = macrophage colony stimulating factor VEGF = vascular endothelial growth factor b-FGF = basic fibroblast growth factor
- Change From Baseline-1 to Day 21-1 in Markers of Angiogenesis (CD31 Staining) [At day 21]
CD31 staining by IHC. For the evaluation of the stain extent, the following semi-quantitative score method (0 to 4) was used: 0, no positive cells; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%. Hence for this scale, the higher the values, the worse is the outcome. For the evaluation of the stain intensity, the following score method (0 to 3) was used: 0, negative; 1, weak; 2, moderate, 3; strong. Also for this scale, the higher the score, the worse the outcome. CD31 is a transmembrane glycoprotein, 130-140 kDa, also know as platelet-endothelium cell adhesion molecule (PECAM-1). CD31 is ligand for CD38 and plays a role in thrombosis and angiogenesis. CD31 is strongly expressed in endothelial cells and weakly expressed in megakaryocytes, platelets, occasional plasma cells, lymphocytes (espc. marginal zone B-cells, peripheral T-cells) and neutrophils.
- Change From Baseline-1 to Day 21-1 in Markers of Autophagy (P62 and LC3B by IHC) [At day 21]
Autophagy is a lysosomal degradation and recycling process implicated in cancer progression and therapy resistance. Labeling of p62 serves as a useful marker for the induction of autophagy, clearance of protein aggregates, and the inhibition of autophagy. Labeling of LC3B serves to track the binding of p62 and subsequent recruitment of autophagosomes. For the evaluation of the extent, the following semi-quantitative score method (0 to 4) was used: 0, no positive cells; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%. Hence for this scale, the higher the values, the worse is the outcome. For the evaluation of the intensity, the following score method (0 to 3) was used: 0, negative; 1, weak; 2, moderate, 3; strong. Also for this scale, the higher the score, the worse the outcome.
Secondary Outcome Measures
- Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax [At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose)]
Once absorbed, reparixin is highly protein bound. By comparing Cmax and AUC for unbound drug to that for total drug, only < 0.1% to 0.2% of reparixin is available as unbound (free) drug. The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. Cmax = Maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units
- Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2 [At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose)]
Once absorbed, reparixin is highly protein-bound. By comparing Cmax and AUC for unbound drug to that for total drug, only < 0.1% to 0.2% of reparixin is available as unbound (free) drug. The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. tmax = Time to reach the maximum plasma concentration obtained directly from the data without interpolation t1/2 = Terminal elimination half-life calculated as ln(2)/ lambda z; calculated only if the coefficient of determination R2 in lambda z estimation is at least 0.8.
- Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21, [At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose)]
The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. AUC0-8 = The area under the plasma concentration-time curve from time 0 to 8 hours post-dose; AUClast = The area under the concentration-time curve from time 0 to last quantifiable concentration AUCtau = The area under the plasma concentration-time curve for dosing interval (dosing interval [tau] = 8 hours); AUCinf = The total area under the plasma concentration-time curve from time zero to time infinity; AUC0-inf = AUClast + Clast/lambda zeta, where Clast is the last observed concentration ≥ lower limit of quantitation at time tlast. All these parameters were calculated by the linear trapezoidal rule.
- Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - CL/F (L/h) at Day 1, CLSS/F (L/h) Day 21) [At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose)]
The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. CL/F = Apparent oral clearance - for DF1681Y only, calculated as dose/AUCinf.; calculated only when the coefficient of determination R2 in lambda zeta estimation is at least 0.8 and percent AUC extrapolation is less than or equal to 20%. CLss/F = Steady state apparent oral clearance - for DF1681Y only calculated as dose/AUCtau.
- Change From Baseline to Day 21 in Leukocytes Subsets [At Day 21]
The Leukocytes subsets analyzed are the following: Lymphocyte in WBC, Total T cell in lymphocytes, B cells in lymphocytes, T-helper cell in lymphocytes, CTL in lymphocytes, NKT cell in lymphocytes, ADCC NK subsets in lymphocytes, Regulatory NK subsets in lymphocytes, Exhausted NK subsets in lymphocytes, CD56-CD16+ NK subsets in lymphocytes, CD11b in PMNs - IL-8, CD18 in PMNs - IL-8, MFI of CD11b - IL-8, MFI of CD66b - IL-8, MFI of CD18 - IL-8, CD11b in PMNs - US, CD18 in PMNs - US, MFI of CD11b - US, MFI of CD66b - US, MFI of CD18 - US, Percent Monocytes expressing IL6 - IL-8,Percent Monocytes expressing IL1b - IL-8, Percent Monocytes expressing IL8 - IL-8, Percent Monocytes expressing TNFa - IL-8, Percent Neutrophils expressing IL6 - IL-8, Percent Neutrophils expressing IL1b - IL-8, Percent Neutrophils expressing IL8 - IL-8, Percent Neutrophils expressing TNFa - IL-8,Percent Monocytes expressing IL6 - US,Percent Monocytes expressing IL1b - US, etc.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Female aged > 18 years.
-
Patients with operable breast cancer, with measurable tumors of more than 1 cm in diameter, that are not candidates for neoadjuvant therapy.
-
Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0-1.
-
No prior treatment by surgery, radiotherapy, hormone therapy e.g. TAMOXIFEN® or RALOXIFEN® for prevention or chemotherapy.
-
Scheduled to undergo definitive local surgery for breast cancer.
-
Patients must be willing to undergo two mandatory tumor biopsies (pre and post therapy) that are not required for standard care. A sample of tumor tissue removed during surgery will also be collected for analysis.
-
Patients must be able to swallow and retain oral medication (intact tablet).
-
Able to undergo all screening assessments outlined in the protocol after giving 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 < upper normal limit (UNL).
-
Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ UNL; alkaline phosphatase (ALP) ≤ UNL; albumin within normal limits.
-
Documented hormone receptor (ER and progesterone receptor) and HER-2- status.
-
No known hepatitis B virus (unless due to immunization), hepatitis C virus, human immune deficiency virus-I and II positive status.
Exclusion Criteria:
-
Male.
-
Pregnancy or lactation or unwillingness to use two adequate methods of birth control throughout the study and for 30 days after study discontinuation.
-
Any other breast cancer types including inflammatory form.
-
Prior surgery to the breast area or primary axillary dissection.
-
Prior treatment for breast cancer.
-
Use of an investigational drug within 30 days preceding the first dose of study medication.
-
Any prior or current cancer, except in situ uterine carcinoma or basocellular cutaneous cancer considered as definitively cured.
-
Any associated medical condition considered incompatible with the study, e.g. cardiac, renal, medullar, respiratory or hepatic insufficiency.
-
Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.
-
Active or uncontrolled infection.
-
Malabsorption syndrome, disease significantly affecting gastrointestinal function.
-
Hypersensitivity to:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Indiana University Simon Cancer Center | Indianapolis | Indiana | United States | 46202-5289 |
| 2 | University of Kansas Cancer Center, 4350 Shawnee Mission Pkwy, Suite 1500, Mailstop 6004 | Fairway | Kansas | United States | 66205 |
| 3 | The Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08903 |
| 4 | Montefiore Medical Center, MMC Medical Park at Eastchester | Bronx | New York | United States | 10461 |
| 5 | Weill Cornell Medical College | New York | New York | United States | 10065 |
| 6 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 7 | Magee-Womens Hospital | Pittsburgh | Pennsylvania | United States | 15213 |
| 8 | Sara Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
| 9 | The Methodist Hospital Research Institute | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Dompé Farmaceutici S.p.A
Investigators
- Principal Investigator: Lori J Goldstein, MD, PhD, Fox Chase Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier:
NCT01861054
Other Study ID Numbers:
- REP0210
First Posted:
May 23, 2013
Last Update Posted:
May 14, 2021
Last Verified:
Apr 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Dompé Farmaceutici S.p.A
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Patients recruitment: before initiating a study, the Investigator was required to have written and dated approval from the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) for the study protocol, written informed consent form (ICF), consent form updates, subject recruitment procedures (e.g., advertisements), and any other written information to be provided to subjects. |
|---|---|
| Pre-assignment Detail | It was planned to enroll 2 sub-groups of patients into the study, Group A: ER+ and/or PR+/HER-2- and Group B: ER-/PR-/HER-2-, and the sample size of 20 patients per group was chosen. Twenty patients in total were enrolled, 18 in Group A and 2 in Group B. The study was closed prematurely due to slow enrollment in group B. All 20 patients were included in the Safety Population and 6 (30%) were included in the PK population. All 20 patients completed the study. |
| Arm/Group Title | ER+ and/or PR+/ HER-2 - | ER-/PR-/HER-2- |
|---|---|---|
| Arm/Group Description | Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack. | Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack. |
| Period Title: Overall Study | ||
| STARTED | 18 | 2 |
| Safety Population | 18 | 2 |
| PK Population | 4 | 2 |
| COMPLETED | 18 | 2 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | ER+ and/or PR+/ HER-2 - | ER-/PR-/HER-2- | Total |
|---|---|---|---|
| Arm/Group Description | Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack | Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack | Total of all reporting groups |
| Overall Participants | 18 | 2 | 20 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
16
88.9%
|
1
50%
|
17
85%
|
| >=65 years |
2
11.1%
|
1
50%
|
3
15%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
54.0
(8.92)
|
56.5
(12.02)
|
54.3
(8.91)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
18
100%
|
2
100%
|
20
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
6
33.3%
|
0
0%
|
6
30%
|
| Not Hispanic or Latino |
12
66.7%
|
2
100%
|
14
70%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
5.6%
|
0
0%
|
1
5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
5.6%
|
0
0%
|
1
5%
|
| White |
15
83.3%
|
2
100%
|
17
85%
|
| More than one race |
1
5.6%
|
0
0%
|
1
5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
18
100%
|
2
100%
|
20
100%
|
Outcome Measures
| Title | Change From Baseline to Day 21 in Markers of Cancer Stem Cells (CSCs) in the Primary Tumor and the Tumoral Microenvironment (ALDH1,CD44/CD24) |
|---|---|
| Description | CSCs were measured in tissue samples by the following techniques: ALDH-1 by ALDEFLUOR and by immunohistochemistry (IHC); CD44/CD24 by flow cytometry or examination of RNA transcripts by RT-PCR and by immunohistochemistry (IHC); epithelial mesenchymal markers (Snail, Twist, Notch) by immunohistochemistry (IHC). |
| Time Frame | At day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis |
| Arm/Group Title | ER+ and/or PR+/ HER-2 - | ER-/PR-/HER-2- |
|---|---|---|
| Arm/Group Description | Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack | Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack |
| Measure Participants | 18 | 2 |
| ALDH+ |
1.34
(2.737)
|
-0.40
(1.131)
|
| CD44+/CD24- |
-0.57
(5.617)
|
0.20
(1.273)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Comparison on ALDH+ cells by ALDEFLUOR assay | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3149 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Comparison on CD44+/CD24- by flow citometry | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8148 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC |
|---|---|
| Description | Pathway markers (AKT, FAK, PTEN and CXCR1) were measured in tissue samples at the pre-study (Day -14 to 0) and Day 21 (or within 24 hours of last dose). For the evaluation of the stain extent, the following semi-quantitative score method (0 to 4) was used: 0, no positive cells; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%. Hence for this scale, the higher the values, the worse is the outcome. For the evaluation of the stain intensity, the following score method (0 to 3) was used: 0, negative; 1, weak; 2, moderate, 3; strong. Also for this scale, the higher the score, the worse the outcome. Serine-threonine protein kinase (AKT, also known as protein kinase B, PKB) Focal adhesion kinase (FAK) Chemokine receptor-1 (CXCR1) |
| Time Frame | Day 21 (or last day of treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis. |
| Arm/Group Title | ER+ and/or PR+/ HER-2 - | ER-/PR-/HER-2- |
|---|---|---|
| Arm/Group Description | Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack | Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack |
| Measure Participants | 18 | 2 |
| Stain Phospho-AKT Extent |
0
|
0
|
| Stain Phospho-AKT Intensity |
0
|
0
|
| Stain AKT Extent |
0
|
1.0
|
| Stain AKT Intensity |
-0.5
|
0
|
| Phospho-FAK Extent |
0
|
0
|
| Phospho-FAK Intensity |
0
|
-1.0
|
| Stain FAK Extent |
0
|
1.0
|
| Stain FAK Intens |
0
|
0
|
| Stain C-PTEN Extent |
0
|
0
|
| Stain C-PTEN Intensity |
0
|
0
|
| Stain D-PTEN Extent |
0
|
0
|
| Stain D-PTEN Intensity |
0
|
0
|
| Stain CXCR1 Extent |
0
|
1.0
|
| Stain CXCR1 Intensity |
-0.5
|
1.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Phospho AKT Extent | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Phospho-AKT Intensity | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | AKT Extent | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2245 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | AKT Intensity | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5785 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Phospho-FAK Extent | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Phospho-FAK Intensity | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3139 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | FAK Extent | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2120 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | FAK Intensity | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | C-PTEN Extent | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | C-PTEN Intensity | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8728 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | D-PTEN Extent | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | D-PTEN Intensity | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8728 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CXCR1 Extent | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2265 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CXCR1 Intensity | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2403 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Change From Baseline to Day 21 in Markers of Inflammation |
|---|---|
| Description | Markers of inflammation (IL-1β, IL-6, IL-8, TNF-α, GM-CSF, VEGF, and b-FGF) were measured in plasma from peripheral blood. IL = interleukins TNF-α = tumor necrosis factor-alpha GM-CSF = macrophage colony stimulating factor VEGF = vascular endothelial growth factor b-FGF = basic fibroblast growth factor |
| Time Frame | At Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis. |
| Arm/Group Title | ER+ and/or PR+/ HER-2 - | ER-/PR-/HER-2- |
|---|---|---|
| Arm/Group Description | Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack | Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack |
| Measure Participants | 18 | 2 |
| Interleukin 1 Beta |
7.019
(30.3118)
|
0
(0.000)
|
| Interleukin 6 |
9.593
(39.2733)
|
0
(0)
|
| Interleukin 8 |
-25.874
(134.3213)
|
29.320
(41.6910)
|
| TNFα |
2.669
(8.0313)
|
-0.890
(3.5780)
|
| GM-CSF |
-2.678
(8.2154)
|
8.705
(12.3107)
|
| VEGF |
253.584
(1120.6125)
|
27.635
(39.0818)
|
| b-FGF |
20.164
(93.4614)
|
-9.750
(13.7886)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Interleukin 1 Beta | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Interleukin 6 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6945 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Interleukin 8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9448 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Tumor Necrosis Factor - alpha | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6292 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Granulocyte Macrophage Colony Stm Factor | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2354 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Vascular Endothelial Growth Factor | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Basic Fibroblast Growth Factor | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4719 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Change From Baseline-1 to Day 21-1 in Markers of Angiogenesis (CD31 Staining) |
|---|---|
| Description | CD31 staining by IHC. For the evaluation of the stain extent, the following semi-quantitative score method (0 to 4) was used: 0, no positive cells; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%. Hence for this scale, the higher the values, the worse is the outcome. For the evaluation of the stain intensity, the following score method (0 to 3) was used: 0, negative; 1, weak; 2, moderate, 3; strong. Also for this scale, the higher the score, the worse the outcome. CD31 is a transmembrane glycoprotein, 130-140 kDa, also know as platelet-endothelium cell adhesion molecule (PECAM-1). CD31 is ligand for CD38 and plays a role in thrombosis and angiogenesis. CD31 is strongly expressed in endothelial cells and weakly expressed in megakaryocytes, platelets, occasional plasma cells, lymphocytes (espc. marginal zone B-cells, peripheral T-cells) and neutrophils. |
| Time Frame | At day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis. |
| Arm/Group Title | ER+ and/or PR+/ HER-2 - | ER-/PR-/HER-2- |
|---|---|---|
| Arm/Group Description | Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack | Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack |
| Measure Participants | 18 | 2 |
| Stain CD31 Extent |
0
|
1.0
|
| Stain CD31 Intensity |
0
|
1.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CD31 Extent | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0951 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CD31 Intensity | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1643 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Change From Baseline-1 to Day 21-1 in Markers of Autophagy (P62 and LC3B by IHC) |
|---|---|
| Description | Autophagy is a lysosomal degradation and recycling process implicated in cancer progression and therapy resistance. Labeling of p62 serves as a useful marker for the induction of autophagy, clearance of protein aggregates, and the inhibition of autophagy. Labeling of LC3B serves to track the binding of p62 and subsequent recruitment of autophagosomes. For the evaluation of the extent, the following semi-quantitative score method (0 to 4) was used: 0, no positive cells; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%. Hence for this scale, the higher the values, the worse is the outcome. For the evaluation of the intensity, the following score method (0 to 3) was used: 0, negative; 1, weak; 2, moderate, 3; strong. Also for this scale, the higher the score, the worse the outcome. |
| Time Frame | At day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis. |
| Arm/Group Title | ER+ and/or PR+/ HER-2 - | ER-/PR-/HER-2- |
|---|---|---|
| Arm/Group Description | Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack | Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack |
| Measure Participants | 18 | 2 |
| Stain P62 Extent |
-1.0
|
0
|
| Stain P62 Intensity |
0
|
-1.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | P62 Extent | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4183 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | P62 Intensity | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3702 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax |
|---|---|
| Description | Once absorbed, reparixin is highly protein bound. By comparing Cmax and AUC for unbound drug to that for total drug, only < 0.1% to 0.2% of reparixin is available as unbound (free) drug. The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. Cmax = Maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units |
| Time Frame | At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Population consisted of patients who received at least one dose of reparixin and had at least one valid, quantifiable PK parameter. This population was used for PK analyses. |
| Arm/Group Title | Treated Patients - Total |
|---|---|
| Arm/Group Description | Patients eligible were treated with Reparixin as add-in monotherapy Reparixin: 1000 mg Oral Reparixin t.i.d. for 21 consecutive days prior to surgery |
| Measure Participants | 6 |
| Day1 - DF1681Y |
62.925
(31.5024)
|
| Day21 - DF1681Y |
63.927
(15.7616)
|
| Day1 - DF1681Y unbound |
145.167
(116.6114)
|
| Day21 - DF1681Y unbound |
136.552
(104.8681)
|
| Day 1 - DF2243Y |
15.788
(2.5240)
|
| Day 21 - DF2243Y |
20.812
(9.9776)
|
| Day 1 - DF2188Y |
7.302
(1.5129)
|
| Day 21 - DF2188Y |
10.367
(4.3439)
|
| Title | Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2 |
|---|---|
| Description | Once absorbed, reparixin is highly protein-bound. By comparing Cmax and AUC for unbound drug to that for total drug, only < 0.1% to 0.2% of reparixin is available as unbound (free) drug. The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. tmax = Time to reach the maximum plasma concentration obtained directly from the data without interpolation t1/2 = Terminal elimination half-life calculated as ln(2)/ lambda z; calculated only if the coefficient of determination R2 in lambda z estimation is at least 0.8. |
| Time Frame | At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Population consisted of patients who received at least one dose of reparixin and had at least one valid, quantifiable PK parameter. This population was used for PK analyses. |
| Arm/Group Title | Treated Patients - Total |
|---|---|
| Arm/Group Description | Patients eligible will be treated with Reparixin as add-in monotherapy Reparixin: 1000 mg Oral Reparixin t.i.d. for 21 consecutive days prior to surgery |
| Measure Participants | 6 |
| Day1 - DF1681Y tmax |
2.667
(2.8752)
|
| Day21 - DF1681Y tmax |
0.997
(0.5508)
|
| Day1 - DF1681Y unbound tmax |
1.583
(1.2813)
|
| Day21 - DF1681Y unbound tmax |
1.092
(0.4903)
|
| Day 1 - DF2243Y tmax |
4.333
(2.3381)
|
| Day 21 - DF2243Y tmax |
2.331
(0.8179)
|
| Day 1 - DF2188Y tmax |
2.500
(1.2247)
|
| Day 21 - DF2188Y tmax |
1.508
(0.5389)
|
| Day1 - DF1681Y t1/2 |
2.090
(0.9847)
|
| Day21 - DF1681Y t1/2 |
1.626
(0.4068)
|
| Day1 - DF1681Y unbound t1/2 |
1.403
(0.4592)
|
| Day21 - DF1681Y unbound t1/2 |
0.989
(0.1683)
|
| Day 1 - DF2243Y t1/2 |
1.913
(0.3268)
|
| Day 21 - DF2243Y t1/2 |
2.575
(0.6442)
|
| Day 1 - DF2188Y t1/2 |
2.035
(1.0618)
|
| Day 21 - DF2188Y t1/2 |
1.575
(0.1953)
|
| Title | Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21, |
|---|---|
| Description | The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. AUC0-8 = The area under the plasma concentration-time curve from time 0 to 8 hours post-dose; AUClast = The area under the concentration-time curve from time 0 to last quantifiable concentration AUCtau = The area under the plasma concentration-time curve for dosing interval (dosing interval [tau] = 8 hours); AUCinf = The total area under the plasma concentration-time curve from time zero to time infinity; AUC0-inf = AUClast + Clast/lambda zeta, where Clast is the last observed concentration ≥ lower limit of quantitation at time tlast. All these parameters were calculated by the linear trapezoidal rule. |
| Time Frame | At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Population consisted of patients who received at least one dose of reparixin and had at least one valid, quantifiable PK parameter. This population was used for PK analyses. |
| Arm/Group Title | Treated Patients - Total |
|---|---|
| Arm/Group Description | Patients eligible will be treated with Reparixin as add-in monotherapy Reparixin: 1000 mg Oral Reparixin t.i.d. for 21 consecutive days prior to surgery |
| Measure Participants | 6 |
| DF1681Y - AUC0-8 - Day 1 |
189.357
(60.2362)
|
| DF1681Y - AUC0-8 - Day 21 |
174.303
(29.8012)
|
| DF1681Y unbound- AUC0-8 - Day 1 |
222.602
(128.0328)
|
| DF1681Y unbound- AUC0-8 - Day 21 |
233.382
(166.0402)
|
| DF2243Y - AUC0-8 - Day 1 |
78.469
(18.8116)
|
| DF2243Y - AUC0-8 - Day 21 |
105.001
(58.2634)
|
| DF2188Y - AUC0-8 - Day 1 |
31.040
(7.9369)
|
| DF2188Y - AUC0-8 - Day 21 |
33.395
(13.2129)
|
| DF1681Y - AUCinf - Day 1 |
211.243
(71.4823)
|
| DF1681Y - AUCinf - Day 21 |
182.479
(36.1551)
|
| DF1681Y unbound - AUCinf - Day 1 |
235.152
(180.1547)
|
| DF1681Y unbound - AUCinf - Day 21 |
234.547
(166.3017)
|
| DF2243Y - AUCinf - Day 1 |
71.297
(25.6857)
|
| DF2243Y - AUCinf - Day 21 |
129.275
(74.5406)
|
| DF2188Y - AUCinf - Day 1 |
31.669
(11.2792)
|
| DF2188Y - AUCinf - Day 21 |
35.092
(13.9473)
|
| DF1681Y - AUClast - Day 1 |
189.319
(60.2817)
|
| DF1681Y - AUClast - Day 21 |
172.296
(28.1847)
|
| DF1681Y unbound - AUClast - Day 1 |
222.078
(128.1305)
|
| DF1681Y unbound - AUClast - Day 21 |
231.235
(167.0377)
|
| DF2243Y - AUClast - Day 1 |
76.821
(17.3033)
|
| DF2243Y - AUClast - Day 21 |
97.360
(46.6809)
|
| DF2188Y - AUClast - Day 1 |
31.028
(7.9336)
|
| DF2188Y - AUClast - Day 21 |
35.433
(12.8434)
|
| DF1681Y - AUCtau - Day 21 |
174.303
(29.8012)
|
| DF1681Y unbound - AUCtau - Day 21 |
233.382
(166.0402)
|
| DF2243Y - AUCtau - Day 21 |
105.001
(58.2634)
|
| DF2188Y - AUCtau - Day 21 |
33.395
(13.2129)
|
| Title | Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - CL/F (L/h) at Day 1, CLSS/F (L/h) Day 21) |
|---|---|
| Description | The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. CL/F = Apparent oral clearance - for DF1681Y only, calculated as dose/AUCinf.; calculated only when the coefficient of determination R2 in lambda zeta estimation is at least 0.8 and percent AUC extrapolation is less than or equal to 20%. CLss/F = Steady state apparent oral clearance - for DF1681Y only calculated as dose/AUCtau. |
| Time Frame | At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK Population consisted of patients who received at least one dose of reparixin and had at least one valid, quantifiable PK parameter. This population was used for PK analyses. |
| Arm/Group Title | Treated Patients - Total |
|---|---|
| Arm/Group Description | Patients eligible will be treated with Reparixin as add-in monotherapy Reparixin: 1000 mg Oral Reparixin t.i.d. for 21 consecutive days prior to surgery |
| Measure Participants | 6 |
| DF1681Y - CL/F - Day 1 |
5.173
(1.7466)
|
| DF1681Y - CLSS/F - Day 21 |
5.866
(0.9086)
|
| DF1681Y unbound - CL/F - Day 1 |
7156.189
(6334.8463)
|
| DF1681Y unbound - CLSS/F - Day 21 |
5604.781
(2335.8016)
|
| Title | Change From Baseline to Day 21 in Leukocytes Subsets |
|---|---|
| Description | The Leukocytes subsets analyzed are the following: Lymphocyte in WBC, Total T cell in lymphocytes, B cells in lymphocytes, T-helper cell in lymphocytes, CTL in lymphocytes, NKT cell in lymphocytes, ADCC NK subsets in lymphocytes, Regulatory NK subsets in lymphocytes, Exhausted NK subsets in lymphocytes, CD56-CD16+ NK subsets in lymphocytes, CD11b in PMNs - IL-8, CD18 in PMNs - IL-8, MFI of CD11b - IL-8, MFI of CD66b - IL-8, MFI of CD18 - IL-8, CD11b in PMNs - US, CD18 in PMNs - US, MFI of CD11b - US, MFI of CD66b - US, MFI of CD18 - US, Percent Monocytes expressing IL6 - IL-8,Percent Monocytes expressing IL1b - IL-8, Percent Monocytes expressing IL8 - IL-8, Percent Monocytes expressing TNFa - IL-8, Percent Neutrophils expressing IL6 - IL-8, Percent Neutrophils expressing IL1b - IL-8, Percent Neutrophils expressing IL8 - IL-8, Percent Neutrophils expressing TNFa - IL-8,Percent Monocytes expressing IL6 - US,Percent Monocytes expressing IL1b - US, etc. |
| Time Frame | At Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis |
| Arm/Group Title | ER+ and/or PR+/ HER-2 - | ER-/PR-/HER-2- |
|---|---|---|
| Arm/Group Description | Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack. | Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack. |
| Measure Participants | 16 | 1 |
| Lymphocyte in WBC |
-2.51
(9.099)
|
-3.70
(NA)
|
| Total T cell in lymphocytes |
1.28
(4.602)
|
-2.80
(NA)
|
| B cell in lymphocytes |
2.678
(7.5565)
|
43.190
(NA)
|
| T-helper cell in lymphocytes |
-1.44
(5.158)
|
-24.90
(NA)
|
| CTL in lymphocytes |
-0.639
(5.5106)
|
-24.100
(NA)
|
| NKT cell in lymphocytes |
0.510
(1.5759)
|
0.140
(NA)
|
| ADCC NK subsets in lymphocytes |
0.727
(4.1787)
|
1.430
(NA)
|
| Regulatory NK subsets in lymphocytes |
-1.358
(3.2465)
|
0.370
(NA)
|
| Exhausted NK subsets in lymphocytes |
-0.177
(1.7006)
|
-0.170
(NA)
|
| CD56-CD16+ NK subsets in lymphocytes |
0.708
(1.6772)
|
0.310
(NA)
|
| CD11b in PMNs - IL-8 |
-1.48
(4.877)
|
-11.60
(NA)
|
| CD18 in PMNs - IL-8 |
-0.23
(4.104)
|
2.10
(NA)
|
| MFI of CD11b - IL-8 |
-1.63
(2.205)
|
3.50
(NA)
|
| MFI of CD66b - IL-8 |
-3.9
(507.79)
|
-929.0
(NA)
|
| MFI of CD18 - IL-8 |
-13.0
(495.89)
|
71.0
(NA)
|
| CD11b in PMNs - US |
1.56
(9.515)
|
-4.20
(NA)
|
| CD18 in PMNs - US |
-5.758
(23.7696)
|
-0.400
(NA)
|
| MFI of CD11b - US |
-0.84
(1.571)
|
-0.30
(NA)
|
| MFI of CD66b - US |
35.1
(536.54)
|
-757.0
(NA)
|
| MFI of CD18 - US |
-105.64
(679.547)
|
-47.00
(NA)
|
| Percent Monocytes expressing IL6 - IL-8 |
8.40590
(27.654326)
|
0.52600
(NA)
|
| Percent Monocytes expressing IL1b - IL-8 |
8.27479
(24.364503)
|
0.32600
(NA)
|
| Percent Monocytes expressing IL8 - IL-8 |
-0.35947
(3.983235)
|
-0.04400
(NA)
|
| Percent Monocytes expressing TNFa - IL-8 |
0.40504
(1.906309)
|
-0.39900
(NA)
|
| Percent Neutrophils expressing IL6 - IL-8 |
2.83019
(26.145843)
|
0.36340
(NA)
|
| Percent Neutrophils expressing IL1b - IL-8 |
10.24530
(32.068081)
|
0.33400
(NA)
|
| Percent Neutrophils expressing IL8 - IL-8 |
0.04596
(1.667000)
|
0.05742
(NA)
|
| Percent Neutrophils expressing TNFa - IL-8 |
0.35635
(2.269023)
|
0.03500
(NA)
|
| Percent Monocytes expressing IL6 - US |
9.77675
(29.705447)
|
0.26500
(NA)
|
| Percent Monocytes expressing IL1b - US |
5.58031
(28.862940)
|
1.03400
(NA)
|
| Percent Monocytes expressing IL8 - US |
0.14087
(2.716051)
|
-0.27600
(NA)
|
| Percent Monocytes expressing TNFa - US |
-0.11532
(1.333406)
|
0.28200
(NA)
|
| Percent Neutrophils expressing IL6 - US |
5.50297
(21.932274)
|
0.59260
(NA)
|
| Percent Neutrophils expressing IL1b - US |
9.28329
(33.754437)
|
1.36450
(NA)
|
| Percent Neutrophils expressing IL8 - US |
0.45567
(2.053990)
|
0.15020
(NA)
|
| Percent Neutrophils expressing TNFa - US |
0.46929
(2.876200)
|
0.54910
(NA)
|
| Percent Monocytes expressing IL6 - LPS |
-0.23
(8.015)
|
-9.60
(NA)
|
| Percent Monocytes expressing IL1b - LPS |
-5.18
(18.237)
|
27.80
(NA)
|
| Percent Monocytes expressing IL8 - LPS |
-4.2057
(21.72201)
|
-74.3700
(NA)
|
| Percent Monocytes expressing TNFa - LPS |
-3.145
(8.8075)
|
-56.400
(NA)
|
| Percent Neutrophils expressing IL6 - LPS |
-2.0310
(4.60857)
|
72.3690
(NA)
|
| Percent Neutrophils expressing IL1b - LPS |
-1.68086
(5.470114)
|
78.19200
(NA)
|
| Percent Neutrophils expressing IL8 - LPS |
0.14986
(1.844687)
|
1.18700
(NA)
|
| Percent Neutrophils expressing TNFa - LPS |
0.1497
(1.97537)
|
1.7720
(NA)
|
| Percent Monocytes expressing IL6 - LPS+IL-8 |
-3.42
(6.783)
|
1.20
(NA)
|
| Percent Monocytes expressing IL1b - LPS+IL-8 |
-4.79
(14.168)
|
25.90
(NA)
|
| Percent Monocytes expressing IL8 - LPS+IL-8 |
-7.738
(12.9421)
|
-76.990
(NA)
|
| Percent Monocytes expressing TNFa - LPS+IL-8 |
-0.3018
(9.97119)
|
-57.9100
(NA)
|
| Percent Neutrophils expressing IL6 - LPS+IL-8 |
1.2629
(20.77484)
|
62.7900
(NA)
|
| Percent Neutrophils expressing IL1b - LPS+IL-8 |
0.1980
(27.96300)
|
81.6290
(NA)
|
| Percent Neutrophils expressing IL8 - LPS+IL-8 |
0.0348
(1.81583)
|
1.0010
(NA)
|
| Percent Neutrophils expressing TNFa - LPS+IL-8 |
-0.0349
(1.75308)
|
2.6490
(NA)
|
| Percent FITC eColi Control |
4.327
(7.7795)
|
-8.500
(NA)
|
| Percent FITC eColi Test |
-1.056
(3.6456)
|
-4.200
(NA)
|
| Percent PMNs unstimulated |
-5.025
(16.3554)
|
28.690
(NA)
|
| Percent PMNs fMLP |
9.152
(18.2092)
|
23.300
(NA)
|
| Percent L-selectin unstimulated |
4.341
(25.8071)
|
-25.000
(NA)
|
| Percent L-selectin fMLP |
-0.2845
(0.95877)
|
-0.2460
(NA)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Lymphocyte in WBC | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6168 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Total T cell in lymphocytes | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6168 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | B cell in lymphocytes | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1453 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | T-helper cell in lymphocytes | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1453 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CTL in lymphocytes | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1453 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | NKT cell in lymphocytes | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | ADCC NK subsets in lymphocytes | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7634 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Regulatory NK subsets in lymphocytes | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5487 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Exhausted NK subsets in lymphocytes | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CD56-CD16+ NK subsets in lymphocytes | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CD11b in PMNs - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1451 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CD18 in PMNs - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2779 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | MFI of CD11b - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1444 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | MFI of CD66b - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1453 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | MFI of CD18 - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9200 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CD11b in PMNs - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2779 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | CD18 in PMNs - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6164 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | MFI of CD11b - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | MFI of CD66b - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2032 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | MFI of CD18 - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL6 - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5250 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL1b - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6706 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL8 - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8312 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing TNFa - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3992 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL6 - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2952 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL1b - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3992 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL8 - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2952 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing TNFa - IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5250 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL6 - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3992 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL1b - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2952 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL8 - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.9999 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing TNFa - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3992 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 33
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL6 - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3992 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 34
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL1b - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2952 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 35
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL8 - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3992 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 36
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing TNFa - US | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2952 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 37
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL6 - LPS | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2238 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 38
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL1b - LPS | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2238 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 39
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL8 - LPS | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1543 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 40
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing TNFa - LPS | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1547 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 41
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL6 - LPS | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1547 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 42
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL1b - LPS | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1547 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 43
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL8 - LPS | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4314 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 44
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing TNFa - LPS | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3153 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 45
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL6 - LPS+IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4700 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 46
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL1b - LPS+IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1605 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 47
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing IL8 - LPS+IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1605 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 48
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Monocytes expressing TNFa - LPS+IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1605 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 49
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL6 - LPS+IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1547 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 50
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL1b - LPS+IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1547 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 51
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing IL8 - LPS+IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3153 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 52
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent Neutrophils expressing TNFa - LPS+IL-8 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1543 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 53
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent FITC eColi Control | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1601 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 54
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent FITC eColi Test | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2368 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 55
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent PMNs unstimulated | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1605 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 56
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent PMNs fMLP | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4700 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 57
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent L-selectin unstimulated | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3392 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 58
| Statistical Analysis Overview | Comparison Group Selection | ER+ and/or PR+/ HER-2 -, ER-/PR-/HER-2- |
|---|---|---|
| Comments | Percent L-selectin fMLP | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8080 |
| Comments | P-Value is based on two-sample t-test or Wilcoxon Rank-Sum test, where appropriate, comparing the 2 study groups. | |
| Method | t-test, 2 sided | |
| Comments | ||
Adverse Events
| Time Frame | throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Total | |
| Arm/Group Description | This represents the total safety population of 20 patients | |
All Cause Mortality |
||
| Total | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/20 (0%) | |
Serious Adverse Events |
||
| Total | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/20 (5%) | |
| Infections and infestations | ||
| POSTOPERATIVE WOUND INFECTION | 1/20 (5%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Total | ||
| Affected / at Risk (%) | # Events | |
| Total | 15/20 (75%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 1/20 (5%) | |
| Congenital, familial and genetic disorders | ||
| Epidermolysis | 1/20 (5%) | |
| Eye disorders | ||
| Vision blurred | 1/20 (5%) | |
| Gastrointestinal disorders | ||
| Nausea | 5/20 (25%) | |
| Abdominal pain | 2/20 (10%) | |
| Constipation | 2/20 (10%) | |
| Flatulence | 2/20 (10%) | |
| Vomiting | 2/20 (10%) | |
| Abdominal discomfort | 1/20 (5%) | |
| Abdominal distension | 1/20 (5%) | |
| Diarrhoea | 1/20 (5%) | |
| Dry mouth | 1/20 (5%) | |
| Dyspepsia | 1/20 (5%) | |
| General disorders | ||
| Fatigue | 8/20 (40%) | |
| Pain | 2/20 (10%) | |
| Oedema peripheral | 1/20 (5%) | |
| Infections and infestations | ||
| Eye infection | 1/20 (5%) | |
| Infection | 1/20 (5%) | |
| Injury, poisoning and procedural complications | ||
| Procedural pain | 5/20 (25%) | |
| Incision site haemorrhage | 1/20 (5%) | |
| Incision site pain | 1/20 (5%) | |
| Post procedural haematoma | 1/20 (5%) | |
| Investigations | ||
| Aspartate aminotransferase increased | 1/20 (5%) | |
| Blood alkaline phosphatase increased | 1/20 (5%) | |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 1/20 (5%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Melanocytic naevus | 1/20 (5%) | |
| Nervous system disorders | ||
| Headache | 3/20 (15%) | |
| Dizziness | 2/20 (10%) | |
| Paraesthesia | 2/20 (10%) | |
| Pheripheral sensory neuropathy | 1/20 (5%) | |
| Psychiatric disorders | ||
| Insomnia | 3/20 (15%) | |
| Anxiety | 1/20 (5%) | |
| Mood swings | 1/20 (5%) | |
| Reproductive system and breast disorders | ||
| Breast mass | 1/20 (5%) | |
| Breast pain | 1/20 (5%) | |
| Pelvic pain | 1/20 (5%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 1/20 (5%) | |
| nasal congestion | 1/20 (5%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash | 2/20 (10%) | |
| Petechiae | 1/20 (5%) | |
| Pruritus | 1/20 (5%) | |
| Rash macular | 1/20 (5%) | |
| Vascular disorders | ||
| Hot flush | 1/20 (5%) | |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Pier Adelchi Ruffini, MD |
|---|---|
| Organization | Dompé Farmaceutici |
| Phone | +39 (0)2 583831 |
| info@dompe.it |
Responsible Party:
Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier:
NCT01861054
Other Study ID Numbers:
- REP0210
First Posted:
May 23, 2013
Last Update Posted:
May 14, 2021
Last Verified:
Apr 1, 2021