Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks

Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks
Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day

Transdermal Estradiol

Sex: Female, Male

Race and Ethnicity Not Collected

0 participants were measured because the study was terminated

Absolute Change in 24 Hour Urinary Calcium Excretion

0 participants were analyzed because the study was terminated

Serum 1,25-dihydroxyvitamin D3

Not available because the study was terminated

Serum Bone Morphogenetic Protein 2

Serum Sclerostin

Serum Estradiol

Serum Total Calcium

Calculated Serum Ionized Calcium

Calculated Tubular Resorption of Calcium

Serum 25 Hydroxyvitamin D

Serum Parathyroid Hormone

Serum Phosphorus

Serum Osteocalcin

Serum Bone-specific Alkaline Phosphatase

Serum C-telopeptides of Type 1 Collagen

It is not available because the study was terminated

Serum Procollagen Type 1 N-terminal Propeptide

Overall Study

Murray J. Favus

Hypercalciuria

Hypercalciuria, Familial Idiopathic

Osteopenia

Osteoporosis

4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day

Transdermal estradiol

The University of Chicago

The Effects of Estrogen Replacement Therapy in Postmenopausal Women With Hypercalciuria and Low Bone Mass

University of Chicago

Pancreatic Cancer

Gemcitabine will be administered for 2 weekly doses every 3 weeks commencing 12 weeks prior to stereotactic radiosurgery as follows:
Gemcitabine 1,000 mg/m2 IV over 30 minutes on Day 1, and 8 of 21- day cycle. This will be done for up to 4 cycles.

Gemcitabine

Capecitabine will be taken orally twice daily on days 1-14 every 3 weeks for 4 cycles (12 weeks) prior to stereotactic radiosurgery as follows:
Capecitabine 650 mg/m2 twice daily for days 1-14 every 3 weeks for up to 4 cycles.

Capecitabine

Fractionated SBRT will be delivered to patients that have stable disease, partial response, or complete response after chemo in the following manner:
12 Gy x 3 fractions (36 Gy total) This will be given every other day.

Stereotactic Body Radiation Therapy (SBRT)

UPMC Cancer Centers

Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma

Induction Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma A Prospective Evaluation in Patients With Locally Advanced Pancreas Cancer

In this study, LPFS is defined as the time from enrollment to first documentation of progressive disease (PD) in the target lesion. Death or development of distant disease is not regarded as an event. For patients that undergo surgical resection, local progression will be defined as disease recurrence detected on follow-up imaging (CT or FDG-PET/CT) that is located within the SBRT target volume.

TTP is defined as the time from enrollment to disease progression. Disease progression will be defined as PD in the target volume, or development of distant disease. OS is defined as the length of time from enrollment to confirmed death from any cause.

All patients that undergo attempted surgical evaluation will have their pathology records reviewed and discussed with the operating surgeon to determine margin status. Margins will be classified as negative, close (1-2.5mm), microscopically positive, and grossly positive.

QOL evaluation will be administered prior to SBRT, after completion of SBRT, and at each follow-up. The survey will be the FACT-G

All patients will be monitored for potential treatment-related toxicity throughout treatment as detailed in the schema. Toxicity will be graded according to the CTCAE v4. Acute toxicity is defined as toxicity occurring within 3 months of completion of SBRT. Late toxicity is defined as toxicity occurring greater than 3 months after treatment.

Ideally, all follow-up FDG-PET/CT scans after chemo will be performed on the same scanner to help limit variability in the SUVs detected by different scanners. For those patients with non-FDG avid tumors, their response to therapy will be assessed by CT scan. The most recent consensus recommendations by the NCI on assessing PET response indicate semi-quantitative SUV (standard uptake value) analysis based on lean body mass and/or body surface area be used in determining 18F-FDG uptake. We will use the EORTC 1999 criteria for defining 18F-FDG response

Dwight Heron

Vice Chairman of Clinical Affairs

Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.

¹³C-DM-BT

Sex/Gender, Customized

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Eastern Cooperative Oncology Group (ECOG) Performance Status

Body Mass Index (BMI)

Disease Status

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system.
The specific phenotype, alleles and their associated activity score (AS) assessed were as follows:
Ultrarapid metabolism (UM) or AS=2.0 (*1XN or *2XN), Extensive metabolism (EM) or AS=1.0 (*1, *2, and *2A), Intermediate metabolism (IM) or AS=0.5 (*9, *10, *17 and *41), and Poor metabolism (PM) or AS=0.0 (3, *4, *5, *7, *8, *11, and *12). The distribution of CYP2D6 genotypes grouped by CYP2D6 metabolism phenotype for each participants are summarized below.

Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers

Spearman rank order correlation coefficients were used to assess the strength of the association between CYP2D6 genotype activity score and DM-BT values.

Spearman's Rank Correlation Coefficient Between CYP2D6 Genotype and ¹³Cdextromethorphan Breath Test (DM-BT)

Spearman rank order correlation coefficients were used to assess the strength of the association between CYP2D6 genotype activity score and Endx Css

Spearman's Rank Correlation Coefficient Between CYP2D6 Activity Score and Endoxifen Steady State Concentrations (Endx Css)

Spearman rank order correlation coefficients were used to assess the strength of the association between CYP2D6 genotype activity score and Endx/NDMT ratio

Spearman's Rank Correlation Coefficient Between CYP2D6 Activity Score and Endoxifen/N-desmethyl-tamoxifen (Endx/NDMT) Ratio

Spearman rank order correlation coefficients were used to assess the strength of the association between baseline ¹³Cdextromethorphan breath test (DM-BT) and Endoxifen steady state concentrations (Endx Css)

Spearman's Rank Correlation Coefficient Between Baseline DM-BT and 3 Month Endoxifen Steady State Concentrations

Spearman rank order correlation coefficients were used to assess the strength of the association between baseline ¹³Cdextromethorphan breath test (DM-BT) and Endoxifen/N-desmethyl-tamoxifen (Endx/NDMT) Ratio

Spearman's Rank Correlation Coefficient Between Baseline DM-BT and 3 Month Endoxifen/N-desmethyl-tamoxifen (Endx/NDMT) Ratio

Spearman's Rank Correlation Coefficient Between 3 Month DM-BT and 3 Month Endoxifen Steady State Concentrations

Spearman's Rank Correlation Coefficient Between 6 Month DM-BT and 6 Month Endoxifen Steady State Concentrations

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system.
The specific phenotype, alleles and their associated activity score (AS) assessed were as follows:
Ultrarapid metabolism (UM) or AS=2.0 (*1XN or *2XN), Extensive metabolism (EM) or AS=1.0 (*1, *2, and *2A), Intermediate metabolism (IM) or AS=0.5 (*9, *10, *17 and *41), and Poor metabolism (PM) or AS=0.0 (3, *4, *5, *7, *8, *11, and *12). The median of 3 month Tamoxifen steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Median of 3 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system.
The specific phenotype, alleles and their associated activity score (AS) assessed were as follows:
Ultrarapid metabolism (UM) or AS=2.0 (*1XN or *2XN), Extensive metabolism (EM) or AS=1.0 (*1, *2, and *2A), Intermediate metabolism (IM) or AS=0.5 (*9, *10, *17 and *41), and Poor metabolism (PM) or AS=0.0 (3, *4, *5, *7, *8, *11, and *12). The median of 6 month Tamoxifen steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Median of 6 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system.
The specific phenotype, alleles and their associated activity score (AS) assessed were as follows:
Ultrarapid metabolism (UM) or AS=2.0 (*1XN or *2XN), Extensive metabolism (EM) or AS=1.0 (*1, *2, and *2A), Intermediate metabolism (IM) or AS=0.5 (*9, *10, *17 and *41), and Poor metabolism (PM) or AS=0.0 (3, *4, *5, *7, *8, *11, and *12). The median of 3 month NDMT steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Median of 3 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system.
The specific phenotype, alleles and their associated activity score (AS) assessed were as follows:
Ultrarapid metabolism (UM) or AS=2.0 (*1XN or *2XN), Extensive metabolism (EM) or AS=1.0 (*1, *2, and *2A), Intermediate metabolism (IM) or AS=0.5 (*9, *10, *17 and *41), and Poor metabolism (PM) or AS=0.0 (3, *4, *5, *7, *8, *11, and *12). The median of 6 month NDMT steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Median of 6 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system.
The specific phenotype, alleles and their associated activity score (AS) assessed were as follows:
Ultrarapid metabolism (UM) or AS=2.0 (*1XN or *2XN), Extensive metabolism (EM) or AS=1.0 (*1, *2, and *2A), Intermediate metabolism (IM) or AS=0.5 (*9, *10, *17 and *41), and Poor metabolism (PM) or AS=0.0 (3, *4, *5, *7, *8, *11, and *12). The median of 3 month 4HT steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Median of 3 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system.
The specific phenotype, alleles and their associated activity score (AS) assessed were as follows:
Ultrarapid metabolism (UM) or AS=2.0 (*1XN or *2XN), Extensive metabolism (EM) or AS=1.0 (*1, *2, and *2A), Intermediate metabolism (IM) or AS=0.5 (*9, *10, *17 and *41), and Poor metabolism (PM) or AS=0.0 (3, *4, *5, *7, *8, *11, and *12). The median of 6 month 4HT steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Median of 6 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system.
The specific phenotype, alleles and their associated activity score (AS) assessed were as follows:
Ultrarapid metabolism (UM) or AS=2.0 (*1XN or *2XN), Extensive metabolism (EM) or AS=1.0 (*1, *2, and *2A), Intermediate metabolism (IM) or AS=0.5 (*9, *10, *17 and *41), and Poor metabolism (PM) or AS=0.0 (3, *4, *5, *7, *8, *11, and *12). The median of 3 month Endx Css for each CYP2D6 phenotype group and the corresponding activity score are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Median of 3 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system.
The specific phenotype, alleles and their associated activity score (AS) assessed were as follows:
Ultrarapid metabolism (UM) or AS=2.0 (*1XN or *2XN), Extensive metabolism (EM) or AS=1.0 (*1, *2, and *2A), Intermediate metabolism (IM) or AS=0.5 (*9, *10, *17 and *41), and Poor metabolism (PM) or AS=0.0 (3, *4, *5, *7, *8, *11, and *12). The median of 6 month Endx Css for each CYP2D6 phenotype group and the corresponding activity score are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Median of 6 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score

Dr. Matthew P. Goetz

Breast Cancer

dextromethorphan hydrobromide

tamoxifen citrate

high performance liquid chromatography

laboratory biomarker analysis

pharmacogenomic studies

pharmacological study

fluorescence imaging

Mayo Clinic in Arizona

Mayo Clinic

Breath Test for Women Receiving Tamoxifen in the Prevention or Treatment of Breast Cancer

¹³C - Dextromethorphan (DM) Breath Test for Determination of CYP2D6 Enzyme Activity in Patients Receiving Tamoxifen

National Cancer Institute (NCI)

All Groups

Adverse Events assessed in accordance with CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0.

Number of Participants Experiencing Serious Adverse Events Including But Not Limited to Hospitalizations, Deaths Related to Treatment, or Other Incapacitating Conditions.

Response and progression will be evaluated in this study using measurements from the MRI/CT scans. Measurements will be made of the image slice with the largest cross sectional area. Two orthogonal measures will be made to determine maximal AP and lateral dimensions. Progression of disease will be defined as a greater than 25% increase of largest cross sectional area by two orthogonal measurements, taking as reference the smallest sum recorded since the treatment started or the appearance of one or more new lesions.

Hydroxyurea: Hydroxyurea inhibits DNA synthesis by inhibition of ribonucleotide diphosphate reductase and is a well-known drug used for the treatment of a number of tumor types including head and neck tumors and chronic myelogenous leukemia. It has also been used as an adjuvant for antiretroviral treatment for patients with HIV and as a treatment for polycythemia vera, essential thrombocythemia and sickle cell disease.
Verapamil: Verapamil is another commonly used medication. It is used for the treatment of angina, hypertension, supraventricular arrhythmias, and migraine prophylaxis. Dosing with standard verapamil is 80-120 mg pox three times a day but the sustained release form can be given 120-480mg once or twice each day.

All Participants

Median Progression-free Survival Rates of the Treatment Population.

Dr. Randy Jensen

Cancer

Brain Cancer

Meningioma

Hydroxyurea inhibits DNA synthesis by inhibition of ribonucleotide diphosphate reductase and is a well-known drug used for the treatment of a number of tumor types including head and neck tumors and chronic myelogenous leukemia. It has also been used as an adjuvant for antiretroviral treatment for patients with HIV and as a treatment for polycythemia vera, essential thrombocythemia and sickle cell disease.

Hydroxyurea

Verapamil is another commonly used medication. It is used for the treatment of angina, hypertension, supraventricular arrhythmias, and migraine prophylaxis. Dosing with standard verapamil is 80-120 mg pox three times a day but the sustained release form can be given 120-480mg once or twice each day.

potassium bicarbonate/rak

The Effects of Estrogen Replacement Therapy in Postmenopausal Women With Hypercalciuria and Low Bone Mass

Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma

Breath Test for Women Receiving Tamoxifen in the Prevention or Treatment of Breast Cancer

Combination of Hydroxyurea and Verapamil for Refractory Meningiomas

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