Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Analgesics

Central Nervous System Depressants

Antitussive Agents

Respiratory System Agents

Vasodilator Agents

Anti-Obesity Agents

Vasoconstrictor Agents

Abiraterone Acetate

Prednisone

Levomethorphan

Dextromethorphan

Theophylline

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Phenylpropanolamine

Guaifenesin

Chlorpheniramine, phenylpropanolamine drug combination

Excitatory Amino Acid Antagonists

Neurotransmitter Agents

Analgesics, Opioid

Narcotics

Bronchodilator Agents

Anti-Asthmatic Agents

Phosphodiesterase Inhibitors

Group A will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP2D6 using 2 single doses of dextromethorphan hydrobromide as a probe drug.

Group B will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP1A2 using 2 single doses of theophylline as a probe drug.

Abiraterone acetate 1000 mg tablets administered orally once daily beginning on Cycle 1 Day 1 up to the time of disease progression

Abiraterone acetate

Prednisone 5mg tablets administered orally twice daily beginning on Cycle 1 Day 1 up to the time of disease progression

Dextromethorphan hydrobromide 30 mg capsules administered orally on Cycle 1 Day -8 and Cycle 1 Day 8 under fasting conditions

Dextromethorphan hydrobromide

Theophylline 100 mg tablets administered orally on Cycle 1 Day -8 and Cycle 1 Day 8 under fasting conditions

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to evaluate the effects of multiple doses of abiraterone acetate plus prednisone on the pharmacokinetics (study of what the body does to a drug) of single doses of dextromethorphan hydrobromide and theophylline in patients with castration resistant prostate cancer.

This is an open-label (identity of assigned study drug will be known) study of abiraterone acetate plus prednisone in male patients with metastatic castration-resistant prostate cancer. This study will consist of screening, treatment, and follow-up periods, and will have 2 study groups. Patients in Group A and B will receive daily abiraterone acetate (1000 mg) plus prednisone (5 mg) twice daily beginning on Cycle 1 Day 1 until disease progression. Patients in Group A will take dextromethorphan hydrobromide 30 mg administered orally once daily on Day -8 and Day 8 of Cycle 1. Patients in Group B will take theophylline 100 mg administered orally once daily on Day -8 and Day 8 of Cycle 1. Serial pharmacokinetic samples will be collected and safety will be monitored throughout the study.

A Drug-Drug Interaction Study of Abiraterone Acetate Plus Prednisone With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer

An Abiraterone Acetate Plus Prednisone Drug-Drug Interaction Study With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer

Janssen Research & Development, LLC

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Anticoagulants

Other Dietary Supplements

Tamoxifen

Citric Acid

Sodium Citrate

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Citrate

dextromethorphan hydrobromide

tamoxifen citrate

high performance liquid chromatography

laboratory biomarker analysis

pharmacogenomic studies

pharmacological study

fluorescence imaging

Matthew P. Goetz, M.D.

Donald W. Northfelt, M.D.

RATIONALE: A breath test that measures enzymes may be effective in identifying women in whom tamoxifen may not be effective.

PURPOSE: This clinical trial is studying a breath test to see how well it works in women receiving tamoxifen for the prevention or treatment of breast cancer.

OBJECTIVES:

* To assess the operating characteristics of the ¹³C-dextromethorphan (\^13 C-DM) breath test in identifying women with breast cancer (or at high risk) who are CYP2D6-genotypic poor metabolizers.
* To examine the correlation between CYP2D6 enzyme activity (as measured by the breath test) and plasma endoxifen (and 4-hydroxyTAM) levels in patients who carry one or more CYP2D6 functional alleles.
* To examine the change in CYP2D6 enzyme activity (as measured by the ¹³C-DM breath test), in patients who start a CYP2D6 inhibitor while taking tamoxifen.
* To determine whether CYP2D6 enzyme activity (as measured by the breath test) changes over time (either as a consequence of drug-induced inhibition or other).
* To measure genetic variation in additional genes that are later identified to affect the metabolism, uptake, or distribution of tamoxifen (e.g., SULT1A1, UGT).

OUTLINE: Patients receive tamoxifen citrate for 6 months. \^13C-dextromethorphan breath tests are conducted at baseline and periodically during the 6 months.

13C-dextromethorphan breath test: Patients receive oral Alka-Seltzer® Gold (ASG; citric acid, potassium bicarbonate, and sodium bicarbonate) in water, then, 15 minutes later, another ASG dose and oral ¹³C-dextromethorphan. Patients breathe into a bag 1-2 times, and the is bag sealed. ¹³CO_2 levels in the bags are measured.

Blood samples are collected at baseline and periodically for pharmacogenetic and pharmacokinetic studies by reverse phase HPLC with fluorescence detection.

After completion of study therapy, patients are followed annually for 5 years.

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

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

National Cancer Institute (NCI)

Mayo Clinic

All eligible participants with adverse events data reported. Adverse events data were not available on 7 participants.

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

Age, Continuous

Female

Sex/Gender, Customized

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Eastern Cooperative Oncology Group (ECOG) Performance Status

Body Mass Index (BMI)

Disease Status

Dr. Matthew P. Goetz

EM/UM (*1/*2AXN)

EM/UM (*1/*1XN)

IM/UM (*41/*2AXN)

EM/EM (*1/*1)

EM/EM (*1/*2A)

EM/EM (*1/*2)

EM/EM (*2/*2)

EM/EM (*2A/*2A)

EM/IM (*1/*9)

EM/IM (*1/*10)

EM/IM (*1/*41)

EM/IM (*2A/*9)

EM/IM (*2A/*41)

EM/PM (*1/*3)

EM/PM (*1/*4)

EM/PM (*2/*4)

EM/PM (*2/*4XN)

EM/PM (*2A/*4)

EM/PM (*2A/*5)

EM/PM (*2A/*6)

IM/IM (*41/*41)

IM/PM (*3/*41)

IM/PM (*4/*9)

IM/PM (*4/*10)

IM/PM (*4/*41)

PM/PM (*3/*4)

PM/PM (*4/*4)

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

Baseline

3 Month

6 Month

All eligible participants with DM-BT values.

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

All eligible participants with Endoxifen pharmacokinetics data.

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

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

All eligible participants with DM-BT values and Endoxifen pharmacokinetics data.

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

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

PM/PM

IM/PM

IM/IM

PM/EM

EM/IM

EM/EM

IM/UM

EM/UM

All eligible participants with pharmacokinetic data available. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

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

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

IM/Ultrarapid Metabolism (UM)

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

All eligible participants with Endoxifen pharmacokinetics data. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

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

All eligible participants with pharmacokinetics data. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

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

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

EM/UM (3.0)

IM/UM (2.5)

EM/EM (2.0)

EM/IM (1.5)

IM/IM (1.0)

EM/PM (1.0)

IM/PM (0.5)

PM/PM (0)

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

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

Overall Study

Symptoms and General Pathology

Fatigue

Susan Goodin, PharmD, FCCP, BCOP

RATIONALE: Dextromethorphan may help relieve fatigue in patients with cancer.

PURPOSE: This clinical trial is studying how well dextromethorphan works in treating patients with fatigue caused by cancer.

OBJECTIVES:

Primary

* Assess the effects of dextromethorphan hydrobromide in patients with cancer-related fatigue.

Secondary

* Correlate the changes in cancer-related fatigue with the levels of plasma homocysteine versus red blood cell folate.

OUTLINE: This is a multicenter, open-label, pilot study.

Patients receive oral dextromethorphan hydrobromide 3 times a day on days 1-7. Treatment repeats weekly for up to 3 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Dextromethorphan in Treating Patients With Fatigue Caused by Cancer

A Pilot Trial to Evaluate the Effects of Dextromethorphan in Patients Suffering From Cancer-Related Fatigue

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Drug-Drug Interaction Study of Abiraterone Acetate Plus Prednisone With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer	NCT01017939	Prostate Neopla...	Abiraterone ace... Prednisone Dextromethorpha... Theophylline	18 Years -	Janssen Research & Development, LLC
A Drug-Drug Interaction Study of Abiraterone Acetate Plus Prednisone With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer	NCT01017939	Prostate Neopla...	Abiraterone ace... Prednisone Dextromethorpha... Theophylline	18 Years -	Janssen Research & Development, LLC
Breath Test for Women Receiving Tamoxifen in the Prevention or Treatment of Breast Cancer	NCT00873366	Breast Cancer	dextromethorpha... tamoxifen citra... high performanc... laboratory biom... pharmacogenomic... pharmacological... fluorescence im...	18 Years - 120 Years	Mayo Clinic
Dextromethorphan in Treating Patients With Fatigue Caused by Cancer	NCT00176540	Fatigue Unspecified Adu... Unspecified Chi...	dextromethorpha...	12 Years - 75 Years	Rutgers, The State University of New Jersey
Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced Solid Tumors	NCT01218620	Adult Solid Neo...	Gamma-Secretase... Ketoconazole Rifampin Midazolam Hydro... Omeprazole Tolbutamide Dextromethorpha... Pharmacological... Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Dextromethorphan in Treating Patients With Fatigue Caused by Cancer	NCT00176540	Fatigue Unspecified Adu... Unspecified Chi...	dextromethorpha...	12 Years - 75 Years	Rutgers, The State University of New Jersey

Spots Global Cancer Trial Database for dextromethorphan hydrobromide