Ignite Creation Date:
2024-05-05 @ 11:27 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00049114
Status:
COMPLETED
Last Update Posted:
2013-06-06
First Post:
2002-11-12
Brief Title:
Tipifarnib Doxorubicin and Cyclophosphamide in Treating Women With Locally Advanced Breast Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase I-II Study of R115777 ZARNESTRA Plus Doxorubicin and Cyclophosphamide in Patients With Locally Advanced Breast Cancer and Metastatic Breast Cancer
Status:
COMPLETED
Status Verified Date:
2013-06
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:
Drugs used in chemotherapy such as doxorubicin and cyclophosphamide work in different ways to stop tumor cells from dividing so they stop growing or die Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth Combining tipifarnib with doxorubicin and cyclophosphamide may kill more tumor cells Phase II trial to study the effectiveness of combining tipifarnib with doxorubicin and cyclophosphamide in treating women who have locally advanced breast cancer
Detailed Description:
PRIMARY OBJECTIVES
I Determine the maximum tolerated dose of tipifarnib when administered with doxorubicin and cyclophosphamide in women with metastatic breast cancer non-regional stage IV disease Phase I closed to accrual as of 11904 II Determine the pathologic complete remission rate in patients with locally advanced breast cancer stages IIB IIIA IIIB or IIIC treated with the recommended phase II dose of this regimen
SECONDARY OBJECTIVES
I Determine the clinical complete response rate in patients treated with this regimen
II Determine the toxicity profile of this regimen in these patients III Correlate pretreatment levels of ErbB1 2 3 4 and phosphorylated levels of Akt STAT3 and Erk ½ with clinical response in these patients and with percent inhibition of proliferation Ki-67 and percent induction of apoptosis in post-treatment tumor specimens
IV Correlate percent decrease of farnesyltransferase FTase activity levels HDJ-2 farnesylation phospho-Akt phospho-STAT3 and phospho-Erk ½ with clinical response rates in these patients and with percent inhibition of proliferation Ki-67 and percent inhibition of apoptosis
OUTLINE This is a multicenter dose-escalation study of tipifarnib Patients are stratified according to presence of inflammatory carcinoma yes vs no
PHASE I nonregional stage IV disease closed to accrual as of 11904 Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1 oral tipifarnib twice daily on days 2-7 and filgrastim G-CSF subcutaneously on days 2-13 Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity
PHASE II stage IIB IIIA IIIB or IIIC Patients receive tipifarnib at the MTD and doxorubicin cyclophosphamide and G-CSF as in phase I phase I closed to accrual as of 11904 After the fourth course patients may undergo complete resection
Patients are followed every 3-4 months for 3 years every 6 months for 2 years and then annually thereafter
PROJECTED ACCRUAL Approximately 3-12 patients will be accrued for phase I closed to accrual as of 11904 of this study A total of 21-50 patients will be accrued for phase II of this study
I Determine the maximum tolerated dose of tipifarnib when administered with doxorubicin and cyclophosphamide in women with metastatic breast cancer non-regional stage IV disease Phase I closed to accrual as of 11904 II Determine the pathologic complete remission rate in patients with locally advanced breast cancer stages IIB IIIA IIIB or IIIC treated with the recommended phase II dose of this regimen
SECONDARY OBJECTIVES
I Determine the clinical complete response rate in patients treated with this regimen
II Determine the toxicity profile of this regimen in these patients III Correlate pretreatment levels of ErbB1 2 3 4 and phosphorylated levels of Akt STAT3 and Erk ½ with clinical response in these patients and with percent inhibition of proliferation Ki-67 and percent induction of apoptosis in post-treatment tumor specimens
IV Correlate percent decrease of farnesyltransferase FTase activity levels HDJ-2 farnesylation phospho-Akt phospho-STAT3 and phospho-Erk ½ with clinical response rates in these patients and with percent inhibition of proliferation Ki-67 and percent inhibition of apoptosis
OUTLINE This is a multicenter dose-escalation study of tipifarnib Patients are stratified according to presence of inflammatory carcinoma yes vs no
PHASE I nonregional stage IV disease closed to accrual as of 11904 Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1 oral tipifarnib twice daily on days 2-7 and filgrastim G-CSF subcutaneously on days 2-13 Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity
PHASE II stage IIB IIIA IIIB or IIIC Patients receive tipifarnib at the MTD and doxorubicin cyclophosphamide and G-CSF as in phase I phase I closed to accrual as of 11904 After the fourth course patients may undergo complete resection
Patients are followed every 3-4 months for 3 years every 6 months for 2 years and then annually thereafter
PROJECTED ACCRUAL Approximately 3-12 patients will be accrued for phase I closed to accrual as of 11904 of this study A total of 21-50 patients will be accrued for phase II of this study
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 |
|---|---|---|---|
| 02-05-125 | None | None | None |
| AECM-0205125 | None | None | None |
| NCI-5598 | None | None | None |
| CDR0000257811 | None | None | None |
| N01CM62204 | NIH | None | httpsreporternihgovquickSearchN01CM62204 |