Participants undergo collection of blood samples for histamine level analysis via ELISA.

Bone Pain

Breast Carcinoma Metastatic in the Bone

Biospecimen Collection

Laboratory Biomarker Analysis

Quality-of-Life Assessment

Questionnaire Administration

Wake Forest University Health Sciences

Histamine and Bone Pain Association in Participants With Breast Cancer Metastatic in the Bone

The Role of Histamine in Breast Cancer Bone Pain

To correlate levels of histamine in plasma with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, analysis of variance (ANOVA) will be used. The histamine levels will be transformed to satisfy the conditional normality assumption if needed. Linear regression models will be used to relate histamine levels (outcome variable) with the pain groups (covariate of interest).

Levels of CGRP will be collected. Statistical analysis will correlate CGRP with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used.

Levels of SCF will be collected. Statistical analysis will correlate SCF with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used.

Levels of Ang II will be collected. Statistical analysis will correlate Ang II with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used.

Levels of Ang 1-7 will be collected. Statistical analysis will correlate Ang 1-7 with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used.

Will perform next generation ribonucleic acid (RNA) sequences using whole blood to determine whether histamine system is involved in the development of cancer-induced bone pain (CIBP).

The thickness of the cortical bone within the irradiated volume will be measured.

The change in patient quality of life will be assessed by the visual analogue scale (VAS) pain scale. The total score range is 0-10 with higher scores denoting worse outcomes.

To be measured using the EORTC QLQ-BM22 quality of life questionnaire. It's divided into two categories, giving a single value: symptoms and functions. A high score indicates a high level of symptoms and a high level of functioning. The score range is 22-88.

National Cancer Institute (NCI)

This is a one arm study in which all individuals receive the treatment; therefore there is no allocation or randomization.
Thirty subjects will receive ranitidine to a maximum of 900 mg/day in 2 daily doses for 6 weeks. The dosage target is 8 mg/kg/day, but the range of ranitidine intake will be between 7.5- 9 mg/kg/day. This is due to the formulation of the tablets, sold as 75, 150, and 300mg tablets. The ranitidine will be taken orally.

Cancer

Thirty subjects will receive Ranitidine to a maximum of 900 mg/day in 2 daily oral doses for 6 weeks. The dosage target is 8 mg/kg/day, but the range of ranitidine intake will be between 7.5- 9 mg/kg/day. This is due to the formulation of the tablets, sold as 75, 150, and 300mg tablets.

Ranitidine

Nova Scotia Health Authority

Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity

To determine the effect of histamine 2 receptor antagonists on immune cell function in healthy humans. Frequency and function of B cell, T cell, monocyte, NK cell and MDSC cells will be assessed by flow cytometry and ELISPOT.

To determine the effect of histamine 2 receptor antagonists on immune cell function cross-sectionally. B cell, T cell, monocyte, NK cell and MDSC cells will be assessed by flow cytometry and ELISPOT.

There is no plan to share the IPD with other researchers.

Lisa Barrett

Associate Professor

Dalhousie University

Healthy individuals will be asked to take ranitidine for 6 weeks to determine the effect on peripheral blood immune cells.

Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis in addition to prophylactic naproxen 500 mg orally twice a day (BID) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.

Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis in addition to prophylactic loratadine 10 mg once a day (QD) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.

Participants received adjuvant or neoadjuvant chemotherapy with pegfilgrastim prophylaxis.

Participants received adjuvant or neoadjuvant chemotherapy and pegfilgrastim.

No Prophylaxis

Participants received adjuvant or neoadjuvant chemotherapy and pegfilgrastim in addition to prophylactic naproxen 500 mg orally twice a day (BID) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.

Naproxen 500 mg BID

Participants received adjuvant or neoadjuvant chemotherapy and pegfilgrastim in addition to prophylactic loratadine 10 mg once a day (QD) for 5 days in each of the 4 cycles, beginning on the day of pegfilgrastim administration.

Loratadine 10 mg QD

Total

Sex: Female, Male

Race/Ethnicity, Customized

Bone pain data were captured as part of standard adverse event (AE) reporting.

Percentage of Participants With Bone Pain (All Grades) in Cycle 1

Percentage of Participants With Bone Pain (All Grades) by Cycle (2-4) and Across Cycles

Bone pain data were captured as part of standard adverse event reporting. Severe bone pain is defined as grade 3 or 4 according to common terminology criteria for adverse events (CTCAE) version 3 grading criteria: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, and Grade 4 = Life-threatening or disabling.

Percentage of Participants With Severe Bone Pain by Cycle and Across Cycles

Participants completed a brief bone pain survey once per day for 5 days beginning the day they received their pegfilgrastim injection. The bone pain survey collected the severity of pain using a 0 (no pain) to 10 (worst pain) scale. Mean patient-reported bone pain values are the average of each participant's bone pain values across survey days 1-5 within each cycle. Across all cycles the mean is the average of each patient-reported bone pain value across all survey days 1-5 and across all cycles. An analysis of variance (ANOVA) model with treatment as explanatory term was used.

Mean Patient-reported Bone Pain by Cycle and Across Cycles

Participants completed a brief bone pain survey once per day for 5 days beginning the day they received their pegfilgrastim injection. The bone pain survey collected the severity of pain using a 0 (no pain) to 10 (worst pain) scale. Maximum patient-reported bone pain is the maximum of each participant's bone pain values across survey Days 1-5 within each cycle. Across all cycles the maximum is the maximum of each patient-reported bone pain value across all survey days 1-5 and across all cycles. An ANOVA model with treatment as explanatory term was used.

Maximum Patient-reported Bone Pain by Cycle and Across Cycles

Patient-reported bone pain AUC was calculated using the trapezoidal rule with bone pain scores from day 1 to 5 for each cycle. The AUC across cycles is the average of AUCs across the cycle.

Area Under the Curve (AUC) for Patient-reported Bone Pain

Severity was graded using CTCAE version 3. A serious adverse event (SAE) is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal; • life threatening; • requires in-patient hospitalization or prolongation of existing hospitalization; • results in persistent or significant disability/incapacity; • congenital anomaly/birth defect; • other medically important serious event.
The investigator assessed each adverse event for relatedness to investigational product(s) or other protocol-required therapies.

Number of Participants With Adverse Events (AEs)

Overall Study

Study Director

No Prophylactic Intervention

Naproxen 500mg BID

Loratadine 10mg QD

Bone Pain in Stage I - III Breast Cancer

Naproxen

Loratadine

Commercially available pegfilgrastim (Neulasta®) will be used in the study, and is considered background therapy. Pegfilgrastim is administered as a single 6 mg subcutaneous injection 24 hours to 72 hours after completion of chemotherapy.

Pegfilgrastim

The choice of chemotherapy regimen (agent, dose, and schedule) is at the discretion of the treating physician.

Chemotherapy

Research Site

NOLAN: Naproxen or Loratadine and Neulasta

Randomized, Phase 2 Study to Estimate the Effect of Prophylactic Intervention With Naproxen or Loratadine on Bone Pain in Breast Cancer Subjects Receiving Chemotherapy and Pegfilgrastim

Amgen

Patients receiving chemotherapy (anthracycline-based) will be randomized to esomeprazole for Cycle 1 Days 1-5 and Cycle 2 Days 1-5

Subjects will be given placebo Cycle 1 Days 1-5 and Cycle 2 Days 1-5.

Subjects will be given esomeprazole 40mg daily by mouth for Cycle 1 Days 1-5 and Cycle 2 Days 1-5.

Esomeprazole

Subjects will be given placebo(surgar pill) 40mg daily by mouth for Cycle 1 Days 1-5 and Cycle 2 Days 1-5.

Sugar Pill

Age, Customized

Proportion of patients who exhibit no more than one emetic episode and who do not require rescue medication for nausea from 2-7 days following chemotherapy. Thus, we will look at esomeprazole when used to decrease the incidence,severity and duration of nausea/vomiting/retching in breast cancer patients who are receiving anthracycline-based chemotherapy.

The first dose of esomeprazole 40 mg will be administrated prior to the initiation of chemotherapy along with the standard antiemetics for each cycle. On day 2 to 5 following chemotherapy, the patient will take one capsule each morning.

The frist dose of sugar pill 40 mg will be administrated prior to the initiation of chemotherapy along with the standard antiemetics for each cycle. On day 2 to 5 following chemotherapy, the patient will take one capsule each morning.

Number of Times a Subject Felt Sick to Her Stomach and Number of Times a Subject Required Rescue Medication

Mothaffar Rimawi

The frist dose of esomeprazole 40 mg will be administrated prior to the initiation of chemotherapy along with the standard antiemetics for each cycle. On day 2 to 5 following chemotherapy, the patient will take one capsule each morning.

Nausea

esomeprazole

Placebo 1 pill daily Cycle 1 Days 1-5 and Cycle 2 Days 1-5

histamine/breast neoplasms

Histamine and Bone Pain Association in Participants With Breast Cancer Metastatic in the Bone

Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity

NOLAN: Naproxen or Loratadine and Neulasta

Nexium Study To Suppress Nausea During Chemotherapy

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