Ignite Creation Date:
2024-05-05 @ 4:57 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00352872
Status:
TERMINATED
Last Update Posted:
2018-03-02
First Post:
2006-07-13
Brief Title:
Pharmacogenetics as a Predictor of Toxicity in Pre-Menopausal Women Receiving Doxorubicin and Cyclophosphamide in Early Breast Cancer
Sponsor:
Indiana University School of Medicine
Organization:
Indiana University
Study Overview
Official Title:
A Pilot Study of Cytochrome P450 Pharmacogenetics as a Predictor of Toxicity in Pre-Menopausal Women Receiving Doxorubicin and Cyclophosphamide in Early Breast Cancer
Status:
TERMINATED
Status Verified Date:
2018-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
This study has been difficult to recruit
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this pilot study is to delineate the role of genetic variations in premature menopause hot flashes and other toxicities in a cohort of premenopausal women with early breast cancer
Primary Objective- To ascertain the effect of common variant alleles of CYP450 2B6 2C19 2C9 and 3A5 in pre-menopausal women with breast cancer receiving anthracycline and cyclophosphamide based chemotherapy as it relates to occurrence of premature menopause defined as more than 12 months of amenorrhea and serum estradiol and FSH levels consistent with post-menopausal status
Secondary Objective 1- To obtain pilot data on the effect of common variant alleles of CYP450 2B6 2C19 2C9 and 3A5 in pre-menopausal women with breast cancer receiving anthracycline and cyclophosphamide based chemotherapy as it relates to occurrence of hot flash frequency and other common toxicities of therapy requiring dose delay or reduction
Secondary Objective 2- To obtain pilot data on the correlation of hot flashes with serum levels of serotonin tryptophan and their metabolites and with polymorphisms of the serotonin transporter and receptor genes
Primary Objective- To ascertain the effect of common variant alleles of CYP450 2B6 2C19 2C9 and 3A5 in pre-menopausal women with breast cancer receiving anthracycline and cyclophosphamide based chemotherapy as it relates to occurrence of premature menopause defined as more than 12 months of amenorrhea and serum estradiol and FSH levels consistent with post-menopausal status
Secondary Objective 1- To obtain pilot data on the effect of common variant alleles of CYP450 2B6 2C19 2C9 and 3A5 in pre-menopausal women with breast cancer receiving anthracycline and cyclophosphamide based chemotherapy as it relates to occurrence of hot flash frequency and other common toxicities of therapy requiring dose delay or reduction
Secondary Objective 2- To obtain pilot data on the correlation of hot flashes with serum levels of serotonin tryptophan and their metabolites and with polymorphisms of the serotonin transporter and receptor genes
Detailed Description:
There is a clear survival benefit with the use of adjuvant cytotoxic therapy for most women with invasive breast cancer even in those who have hormone receptor positive disease and receive adjuvant hormonal therapy with tamoxifen1 In addition several trials have shown a benefit for anthracycline based regimens over the more classic combination of cyclophosphamide methotrexate and 5-fluorouracil1-4 The improved efficacy with taxanes in the adjuvant setting has more recently been demonstrated for patients with lymph-node positive disease5-8 Despite clear survival benefits with cytotoxic therapy the 10 year-disease specific mortality remains suboptimal at 69-78 and 49-53 for patients with and without lymph node involvement respectively9
Of the 180000 women diagnosed with breast cancer in the United States about one-fourth are pre-menopausal10-13 Breast cancer clearly represents one of the most commonly diagnosed malignancies in this patient population With the common use of adjuvant chemotherapy long-term sequelae of treatment are becoming increasingly important In addition to the acute toxicities of anthracycline and cyclophosphamide-based regimens5 one side effect with both psycho-social and physical implications is pre-mature menopause13-17 The frequency of menopause induced by poly-agent chemotherapy ranges from 34-89161819 Multiple factors both patient and drug-related play a role in explaining this large variability The age of the patient at time of therapy131920 type of chemotherapy drugs1821 and duration and intensity22 of therapy all influence the overall likelihood of a patient prematurely entering menopause after therapy In a previously reported study age and systemic therapy were important variables in determining menopause in women with loco-regional breast cancer in multivariate analysis19 Women with advancing age had a higher rate of menopause as expected Hormonal therapy and to a much greater degree systemic therapy predicted early menopause The combination of systemic and hormonal therapy appeared to have an additive effect on induction of menopause Of importance however the added impact of hormonal therapy when added to cytotoxic therapy appears to play a minimal role in the induction of menopause when compared to cytotoxic therapy alone It is also likely that intrinsic host genetic variability may also play a role as well The variable ability to metabolize and clear a drug may in part affect efficacy and toxicity of these drugs and may ultimately impact the effect of the drug on ovarian function One important example of this relates to polymorphisms in enzymes important in the clearance of the described drugs To date little work has been done to understand the importance of inter-individual host specific variability on the risk of a breast cancer patient experiencing drug-induced pre-mature menopause
Of the 180000 women diagnosed with breast cancer in the United States about one-fourth are pre-menopausal10-13 Breast cancer clearly represents one of the most commonly diagnosed malignancies in this patient population With the common use of adjuvant chemotherapy long-term sequelae of treatment are becoming increasingly important In addition to the acute toxicities of anthracycline and cyclophosphamide-based regimens5 one side effect with both psycho-social and physical implications is pre-mature menopause13-17 The frequency of menopause induced by poly-agent chemotherapy ranges from 34-89161819 Multiple factors both patient and drug-related play a role in explaining this large variability The age of the patient at time of therapy131920 type of chemotherapy drugs1821 and duration and intensity22 of therapy all influence the overall likelihood of a patient prematurely entering menopause after therapy In a previously reported study age and systemic therapy were important variables in determining menopause in women with loco-regional breast cancer in multivariate analysis19 Women with advancing age had a higher rate of menopause as expected Hormonal therapy and to a much greater degree systemic therapy predicted early menopause The combination of systemic and hormonal therapy appeared to have an additive effect on induction of menopause Of importance however the added impact of hormonal therapy when added to cytotoxic therapy appears to play a minimal role in the induction of menopause when compared to cytotoxic therapy alone It is also likely that intrinsic host genetic variability may also play a role as well The variable ability to metabolize and clear a drug may in part affect efficacy and toxicity of these drugs and may ultimately impact the effect of the drug on ovarian function One important example of this relates to polymorphisms in enzymes important in the clearance of the described drugs To date little work has been done to understand the importance of inter-individual host specific variability on the risk of a breast cancer patient experiencing drug-induced pre-mature menopause
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None