Ignite Creation Date:
2024-05-06 @ 1:22 AM
Last Modification Date:
2024-10-26 @ 11:03 AM
Study NCT ID:
NCT01797120
Status:
COMPLETED
Last Update Posted:
2018-05-30
First Post:
2013-02-14
Brief Title:
Study of Fulvestrant - Everolimus in Post-Menopausal Hormone-Receptor Metastatic Breast Ca Resistant to AI
Sponsor:
PrECOG LLC
Organization:
PrECOG LLC
Study Overview
Official Title:
Randomized Double-Blind Placebo-Controlled Phase II Trial of Fulvestrant Faslodex Plus Everolimus in Post-Menopausal Patients With Hormone-Receptor Positive Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy
Status:
COMPLETED
Status Verified Date:
2018-04
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:
PrE0102
Brief Summary:
Post-menopausal women with hormone-receptor positive HR metastatic breast cancer resistant to aromatase inhibitor AI therapy will be randomized to receive Fulvestrant Faslodex with Everolimus or Fulvestrant Faslodex with a placebo no active ingredients
Fulvestrant has demonstrated activity when used as first second or third line endocrine therapy making it an attractive therapy for combination with other agents In addition it is commonly reserved for use following disease progression on AI therapy
Everolimus is an orally administered drug that blocks a signaling pathway called mTOR mTOR acts as a regulator for many processes in the body including cell growth Blocking this pathway may have an effect on cell growth
The combination of a novel class of agents mTOR inhibitors and an established standard treatment for metastatic HR breast cancer may potentially increase the clinical benefit by targeting multiple different biological pathways
Fulvestrant has demonstrated activity when used as first second or third line endocrine therapy making it an attractive therapy for combination with other agents In addition it is commonly reserved for use following disease progression on AI therapy
Everolimus is an orally administered drug that blocks a signaling pathway called mTOR mTOR acts as a regulator for many processes in the body including cell growth Blocking this pathway may have an effect on cell growth
The combination of a novel class of agents mTOR inhibitors and an established standard treatment for metastatic HR breast cancer may potentially increase the clinical benefit by targeting multiple different biological pathways
Detailed Description:
Breast cancer is the most commonly diagnosed malignancy in women worldwide In the United States an estimated 230480 new cases of invasive breast cancer were diagnosed in 2011 with 39520 breast cancer deaths In 40-80 of women with node-positive disease at diagnosis their breast cancer will recur When distant metastases occur median survival is 18 to 36 months from time of recurrence Among the 60-70 of women with HR breast cancer 40-60 of them will benefit from endocrine therapy Endocrine therapy has shown to yield similar survival rates in hormone-sensitive disease as compared to chemotherapy although response rates are lower and responses develop more slowly Endocrine therapy is considerably less toxic than chemotherapy and is therefore the preferred treatment option for patients with HR disease
Endocrine therapy represents the foundation of treatment for HR metastatic and locally advanced breast cancer Multiple compounds in varying classes exist and those most widely used include the selective estrogen receptor modulators SERMs aromatase inhibitors AIs and the selective estrogen receptor down-regulators SERDs Although the utility of these drugs is well established as many as 50 of women with HR breast cancer will fail to respond to endocrine treatment Moreover those who do respond will inevitably develop acquired resistance
Fulvestrant is the first drug which acts as a pure estrogen receptor ER antagonist without known agonist effects It competitively binds to the ERs with an approximately 100 times greater affinity than that of tamoxifen Fulvestrant promotes the degradation of ERs and subsequently prevents ER-mediated gene transcription
Everolimus RAD001 is an oral derivative of rapamycin that is an m-TOR inhibitor At cellular and molecular levels everolimus acts as a signal transduction inhibitor Everolimus selectively inhibits mTOR mammalian target of rapamycin a key and highly conserved serine-threonine kinase which is present in all cells and is a central regulator of protein synthesis and ultimately cell growth cell proliferation angiogenesis and cell survival mTOR is the only currently known target of everolimus
In oncology everolimus has been in clinical development since 2002 for patients with various hematologic and non-hematologic malignancies as a single agent or in combination with antitumor agents including cytotoxic chemotherapeutic agents targeted therapies antibodies and hormonal agents
Patients will be randomized 11 to receive everolimus or placebo with fulvestrant after consideration of stratification factors of performance status 0 vs 1 measurable disease yes vs no and prior chemotherapy for metastatic disease yes vs no
Patients will be evaluated for disease response every 12 weeks and treated until disease progression or unacceptable toxicity or withdrawal of consent for a maximum of 12 cycles 48 weeks
Patients with no evidence of progressive disease who remain on study after completing 12 cycles are unblinded and continue to receive fulvestrant alone if originally randomized to placebo or in combination with everolimus if originally randomized to everolimus at the same dose and schedule Patients will continue to be evaluated for disease response every 12 weeks and continue until disease progression or unacceptable toxicity
Endocrine therapy represents the foundation of treatment for HR metastatic and locally advanced breast cancer Multiple compounds in varying classes exist and those most widely used include the selective estrogen receptor modulators SERMs aromatase inhibitors AIs and the selective estrogen receptor down-regulators SERDs Although the utility of these drugs is well established as many as 50 of women with HR breast cancer will fail to respond to endocrine treatment Moreover those who do respond will inevitably develop acquired resistance
Fulvestrant is the first drug which acts as a pure estrogen receptor ER antagonist without known agonist effects It competitively binds to the ERs with an approximately 100 times greater affinity than that of tamoxifen Fulvestrant promotes the degradation of ERs and subsequently prevents ER-mediated gene transcription
Everolimus RAD001 is an oral derivative of rapamycin that is an m-TOR inhibitor At cellular and molecular levels everolimus acts as a signal transduction inhibitor Everolimus selectively inhibits mTOR mammalian target of rapamycin a key and highly conserved serine-threonine kinase which is present in all cells and is a central regulator of protein synthesis and ultimately cell growth cell proliferation angiogenesis and cell survival mTOR is the only currently known target of everolimus
In oncology everolimus has been in clinical development since 2002 for patients with various hematologic and non-hematologic malignancies as a single agent or in combination with antitumor agents including cytotoxic chemotherapeutic agents targeted therapies antibodies and hormonal agents
Patients will be randomized 11 to receive everolimus or placebo with fulvestrant after consideration of stratification factors of performance status 0 vs 1 measurable disease yes vs no and prior chemotherapy for metastatic disease yes vs no
Patients will be evaluated for disease response every 12 weeks and treated until disease progression or unacceptable toxicity or withdrawal of consent for a maximum of 12 cycles 48 weeks
Patients with no evidence of progressive disease who remain on study after completing 12 cycles are unblinded and continue to receive fulvestrant alone if originally randomized to placebo or in combination with everolimus if originally randomized to everolimus at the same dose and schedule Patients will continue to be evaluated for disease response every 12 weeks and continue until disease progression or unacceptable toxicity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None