Ignite Creation Date:
2024-05-05 @ 4:48 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00317720
Status:
COMPLETED
Last Update Posted:
2023-10-17
First Post:
2006-04-21
Brief Title:
Trastuzumab and RAD001 in Patients With Human Epidermal Growth Receptor 2 HER-2 Overexpressing Breast Cancer
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
Phase I-II Study of Trastuzumab in Combination With RAD001 in Patients With HER-2 Overexpressing PTEN-deficient Metastatic Breast Cancer Progressing on Trastuzumab-Based Therapy
Status:
COMPLETED
Status Verified Date:
2023-10
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:
Primary Objectives
1 To identify the optimal dose and pharmacokinetics of RAD001 in combination with trastuzumab in a Phase I trial
2 To determine the efficacy of RAD001 plus trastuzumab in HER-2-overexpressing patients with resistance to trastuzumab-based therapy for metastatic breast cancer in a Phase II trial
1 Trastuzumab resistance will be defined as the development of progressive disease after trastuzumab-based therapy for metastatic breast cancer Patients who develop metastases while receiving adjuvant or neoadjuvant trastuzumab will be eligible
2 Efficacy would be measured by the rate of objective response plus stable disease lasting 6 months complete response CR partial response PR stable disease SD
Secondary objectives
1 To determine the pharmacokinetics of RAD001 in combination with trastuzumab In the phase II portion of the study pharmacokinetic studies will be optional
2 To determine the nature and degree of toxicity of RAD001 in combination with trastuzumab in this cohort of patients
3 To determine expression levels of total and phosphorylated mTOR and p70S6K-T389-P as well as relevant downstream signaling components eg S6 4E-BP1 in pre- and post- treatment tumor samples
4 To correlate biomarker expression with response to therapy
1 To identify the optimal dose and pharmacokinetics of RAD001 in combination with trastuzumab in a Phase I trial
2 To determine the efficacy of RAD001 plus trastuzumab in HER-2-overexpressing patients with resistance to trastuzumab-based therapy for metastatic breast cancer in a Phase II trial
1 Trastuzumab resistance will be defined as the development of progressive disease after trastuzumab-based therapy for metastatic breast cancer Patients who develop metastases while receiving adjuvant or neoadjuvant trastuzumab will be eligible
2 Efficacy would be measured by the rate of objective response plus stable disease lasting 6 months complete response CR partial response PR stable disease SD
Secondary objectives
1 To determine the pharmacokinetics of RAD001 in combination with trastuzumab In the phase II portion of the study pharmacokinetic studies will be optional
2 To determine the nature and degree of toxicity of RAD001 in combination with trastuzumab in this cohort of patients
3 To determine expression levels of total and phosphorylated mTOR and p70S6K-T389-P as well as relevant downstream signaling components eg S6 4E-BP1 in pre- and post- treatment tumor samples
4 To correlate biomarker expression with response to therapy
Detailed Description:
RAD001 is a new drug that was designed to block proteins that are important in the development and growth of cancer It may also stop the growth of new blood vessels that help tumor growth resulting in cell death
Trastuzumab is a monoclonal antibody that binds to the HER-2 molecule on the surface of cancer cells It does not bind to cells that do not have the HER-2 molecule Trastuzumab slows the growth of cancer cells and also makes them more able to be treated with other chemotherapy drugs
Before you begin to receive the study drug you will have what are called screening tests These tests will help the doctor decide if you are eligible to take part in this study You will have your complete medical history recorded and a physical exam including measurement of vital signs blood pressure heart rate temperature and breathing rate will be performed Routine blood tests about 2 teaspoons will be collected within 1 week before therapy Cancer tissue taken at the time of your initial diagnosis or surgery will be collected Special stains will be done that will help find ways in which researchers can predict the response of your cancer to trastuzumab plus RAD001 Women who are able to have children must have a negative urine pregnancy test Some participants may need x-rays andor positron emission tomography PET scans before receiving study drug and again within 3 weeks after the start of therapy
If you are found to be eligible to take part in this study you will receive RAD001 tablets by mouth once a day Every 3 weeks 21 days is considered 1 course of the study The dose of trastuzumab you receive on this study will not be different from what you were receiving before this study started
If you are participating in the Phase I portion of the study you will have about 4 teaspoons of blood drawn before you start the study on Day 1 Blood samples will be drawn prior to initiation of treatment and at 05 1 2 5 8 24 hours You will also have around 4 teaspoons of blood drawn on Day 15 before the start of treatment and at 05 1 2 5 8 and 24 hours
While on study you will have weekly blood tests about 2 teaspoons for the first 3 weeks After 3 weeks if you tolerate the study drug well your blood tests about 2 teaspoons each time will be drawn once every 3 weeks or as often as your physicians feel that they are necessary Six 6 weeks after your first cycle of study drug you will undergo x-rays computed tomography CT scans magnetic resonance imaging MRI or PET scans to see how you are responding to the study drug If the disease shows a response to the study drug or is stable then future x-rays CT scans MRI or PET scans will be performed every 6 weeks or as often as the physician feels it is necessary After that the scans will be performed every 9 weeks or as often as the physician feels it is necessary A physical exam including vital signs blood pressure heart rate temperature and breathing rate will be done every 3 weeks and any time the physician feels it is necessary
You will continue to take the study drug as long as you continue to benefit from it You may be removed from this study if you do not respond after 2 courses of the study drug intolerable side effects occur or the disease gets worse Your dose may be lowered if certain side effects occur
Once you come off study a physical exam measurement of vital signs blood pressure heart rate temperature and breathing rate a blood test about 2 teaspoons x-rays andor scans will be done
This is an investigational study Trastuzumab is commercially available for use as a single therapy or in combination with paclitaxel However the combination of trastuzumab and RAD001 is experimental The FDA has authorized RAD001 for use in research only Up to 47 patients will take part in this multicenter study Up to 36 will be enrolled at UT MD Anderson
Trastuzumab is a monoclonal antibody that binds to the HER-2 molecule on the surface of cancer cells It does not bind to cells that do not have the HER-2 molecule Trastuzumab slows the growth of cancer cells and also makes them more able to be treated with other chemotherapy drugs
Before you begin to receive the study drug you will have what are called screening tests These tests will help the doctor decide if you are eligible to take part in this study You will have your complete medical history recorded and a physical exam including measurement of vital signs blood pressure heart rate temperature and breathing rate will be performed Routine blood tests about 2 teaspoons will be collected within 1 week before therapy Cancer tissue taken at the time of your initial diagnosis or surgery will be collected Special stains will be done that will help find ways in which researchers can predict the response of your cancer to trastuzumab plus RAD001 Women who are able to have children must have a negative urine pregnancy test Some participants may need x-rays andor positron emission tomography PET scans before receiving study drug and again within 3 weeks after the start of therapy
If you are found to be eligible to take part in this study you will receive RAD001 tablets by mouth once a day Every 3 weeks 21 days is considered 1 course of the study The dose of trastuzumab you receive on this study will not be different from what you were receiving before this study started
If you are participating in the Phase I portion of the study you will have about 4 teaspoons of blood drawn before you start the study on Day 1 Blood samples will be drawn prior to initiation of treatment and at 05 1 2 5 8 24 hours You will also have around 4 teaspoons of blood drawn on Day 15 before the start of treatment and at 05 1 2 5 8 and 24 hours
While on study you will have weekly blood tests about 2 teaspoons for the first 3 weeks After 3 weeks if you tolerate the study drug well your blood tests about 2 teaspoons each time will be drawn once every 3 weeks or as often as your physicians feel that they are necessary Six 6 weeks after your first cycle of study drug you will undergo x-rays computed tomography CT scans magnetic resonance imaging MRI or PET scans to see how you are responding to the study drug If the disease shows a response to the study drug or is stable then future x-rays CT scans MRI or PET scans will be performed every 6 weeks or as often as the physician feels it is necessary After that the scans will be performed every 9 weeks or as often as the physician feels it is necessary A physical exam including vital signs blood pressure heart rate temperature and breathing rate will be done every 3 weeks and any time the physician feels it is necessary
You will continue to take the study drug as long as you continue to benefit from it You may be removed from this study if you do not respond after 2 courses of the study drug intolerable side effects occur or the disease gets worse Your dose may be lowered if certain side effects occur
Once you come off study a physical exam measurement of vital signs blood pressure heart rate temperature and breathing rate a blood test about 2 teaspoons x-rays andor scans will be done
This is an investigational study Trastuzumab is commercially available for use as a single therapy or in combination with paclitaxel However the combination of trastuzumab and RAD001 is experimental The FDA has authorized RAD001 for use in research only Up to 47 patients will take part in this multicenter study Up to 36 will be enrolled at UT MD Anderson
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