Ignite Creation Date:
2024-05-05 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00134680
Status:
COMPLETED
Last Update Posted:
2014-09-16
First Post:
2005-08-24
Brief Title:
Letrozole Herceptin in Her2neu Estrogen Receptor ER andor Progesterone Receptor PR Positive MBC
Sponsor:
Duke University
Organization:
Duke University
Study Overview
Official Title:
Phase II Trial of the Combination of Letrozole 25 mg Daily and Trastuzumab 2 mgkg Weekly in ErbB2 Positive and Estrogen Receptor andor Progesterone Receptor Positive Metastatic Breast Cancer
Status:
COMPLETED
Status Verified Date:
2012-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of the study is to investigate the effects good and bad that the combination of the drugs letrozole also called Femara and trastuzumab also called Herceptin has on breast cancer The United States US Food and Drug Administration has approved both letrozole and Herceptin for the treatment of advanced breast cancer Doctors hope that the combination will work better than either drug alone
Detailed Description:
Since ER function is regulated by peptide growth factor signaling the phenotype of ER positive tumors may be influenced by the expression of growth factors and growth factor receptors A potential interaction between ErbB2 HER2neu expression and the success of endocrine therapy has been examined ErbB2 expression was shown to correlate with resistance to hormone therapy
An inverse relationship between endocrine therapy responsiveness and ErbB2 expression has not been observed in all studies This may be due to discordant ER status between the primary tumor and metastatic sites ER status can be discordant in approximately 20 of cases with a tendency for metastatic disease to become ER negative with time Data concerning ErbB2 is more limited but there may be similar lack of concordance between primary tumor and metastases
Inhibition of ErbB2 signaling may slow the development of resistance to estrogen deprivation therapy by inhibiting a pathway that promotes estrogen independent growth The ErbB2 signal transduction pathway bypasses the requirement for estrogen for breast epithelial cell growth When ErbB2 is activated in ER positive breast cancer cells in vitro ER becomes phosphorylated and capable of stimulating transcription without estrogen Chronic activation with heregulin a ligand for the ErbB family of receptors leads to ER down-regulation and the acquisition of an ER negative phenotype
Estrogen deprivation therapy with selective aromatase inhibitors SAIs has become the standard of care for postmenopausal women with tamoxifen-resistant advanced breast cancer About 13 of patients benefit from this therapy There is interest in treating endocrine therapy refractory breast cancer with the recombinant DNA-derived humanized monoclonal antibody trastuzumab When given alone trastuzumab has an endocrine therapy-like risk benefit ratio Trastuzumab targets ErbB2 HER2neu Some breast cancers may coexpress ER and ErbB2
Letrozole Femara is a highly selective oral non-steroidal aromatase inhibitor According to in vitro data letrozole is 170-fold more potent in inhibiting aromatase than aminoglutethimide AG and 19-fold more active than anastrozole Letrozole effectively inhibits intratumoral aromatase according to in vitro and in vivo data It is indicated for the treatment of advanced breast carcinoma in post-menopausal women who have failed prior anti-estrogen therapy Final FDA approval was granted in 1997 In two randomized phase IIbIII studies in patients previously treated with an antiestrogen 195 and 236 of patients achieved an objective response with letrozole 25 mgday compared with 124 receiving AG and 164 of patients receiving megace Median overall survival was increased in the letrozole 25 mgday group by 8 months compared to AG and by 3 months compared to megace The lower 05 mgday dose of letrozole was associated with poorer response rates and overall survival in both studies
Trastuzumab Herceptin was approved in 1998 A trial of trastuzumab as a single agent for first line treatment of advanced disease has been reported Response rate in the first 62 patients was 24
The primary objective of this trial is to determine the proportion of patients with ER andor PR positive ErbB2 positive tamoxifen resistant metastatic breast cancer who achieve complete remission or partial remission or no significant change in lesion size for 24 weeks from a combination of letrozole and trastuzumab The study will also determine duration of response and median time to progression evaluate toxicity generate a tumor and serum bank and analyze ErbB2 expression on circulating malignant cells during treatment
The study will enroll 35 patients
An inverse relationship between endocrine therapy responsiveness and ErbB2 expression has not been observed in all studies This may be due to discordant ER status between the primary tumor and metastatic sites ER status can be discordant in approximately 20 of cases with a tendency for metastatic disease to become ER negative with time Data concerning ErbB2 is more limited but there may be similar lack of concordance between primary tumor and metastases
Inhibition of ErbB2 signaling may slow the development of resistance to estrogen deprivation therapy by inhibiting a pathway that promotes estrogen independent growth The ErbB2 signal transduction pathway bypasses the requirement for estrogen for breast epithelial cell growth When ErbB2 is activated in ER positive breast cancer cells in vitro ER becomes phosphorylated and capable of stimulating transcription without estrogen Chronic activation with heregulin a ligand for the ErbB family of receptors leads to ER down-regulation and the acquisition of an ER negative phenotype
Estrogen deprivation therapy with selective aromatase inhibitors SAIs has become the standard of care for postmenopausal women with tamoxifen-resistant advanced breast cancer About 13 of patients benefit from this therapy There is interest in treating endocrine therapy refractory breast cancer with the recombinant DNA-derived humanized monoclonal antibody trastuzumab When given alone trastuzumab has an endocrine therapy-like risk benefit ratio Trastuzumab targets ErbB2 HER2neu Some breast cancers may coexpress ER and ErbB2
Letrozole Femara is a highly selective oral non-steroidal aromatase inhibitor According to in vitro data letrozole is 170-fold more potent in inhibiting aromatase than aminoglutethimide AG and 19-fold more active than anastrozole Letrozole effectively inhibits intratumoral aromatase according to in vitro and in vivo data It is indicated for the treatment of advanced breast carcinoma in post-menopausal women who have failed prior anti-estrogen therapy Final FDA approval was granted in 1997 In two randomized phase IIbIII studies in patients previously treated with an antiestrogen 195 and 236 of patients achieved an objective response with letrozole 25 mgday compared with 124 receiving AG and 164 of patients receiving megace Median overall survival was increased in the letrozole 25 mgday group by 8 months compared to AG and by 3 months compared to megace The lower 05 mgday dose of letrozole was associated with poorer response rates and overall survival in both studies
Trastuzumab Herceptin was approved in 1998 A trial of trastuzumab as a single agent for first line treatment of advanced disease has been reported Response rate in the first 62 patients was 24
The primary objective of this trial is to determine the proportion of patients with ER andor PR positive ErbB2 positive tamoxifen resistant metastatic breast cancer who achieve complete remission or partial remission or no significant change in lesion size for 24 weeks from a combination of letrozole and trastuzumab The study will also determine duration of response and median time to progression evaluate toxicity generate a tumor and serum bank and analyze ErbB2 expression on circulating malignant cells during treatment
The study will enroll 35 patients
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1144-05-6R5 | OTHER | Duke legacy protocol ID | None |