Ignite Creation Date:
2024-05-05 @ 5:07 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00399529
Status:
COMPLETED
Last Update Posted:
2020-04-22
First Post:
2006-11-13
Brief Title:
Trastuzumab Cyclophosphamide and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for the Treatment of HER-2Neu-Overexpressing Metastatic Breast Cancer
Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Organization:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Overview
Official Title:
A Feasibility Study of Combination Therapy With Trastuzumab Cyclophosphamide and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for HER-2Neu-Overexpressing Metastatic Breast Cancer
Status:
COMPLETED
Status Verified Date:
2020-04
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:
None
Brief Summary:
This is a feasibility study to examine combination therapy with Trastuzumab T Cyclophosphamide CY and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine in patients with Stage IV HER-2neu-overexpressing breast cancer The main purposes of this study are to test the safety clinical benefit and bioactivity of vaccine therapy in combination with Cyclophosphamide and Trastuzumab in patients with HER-2neu-overexpressing Stage IV breast cancer This study will also to test whether the Cyclophosphamide can eliminate the suppressive influence of regulatory T cells and whether Trastuzumab can increase antigen processing and presentation These drug activities may make the immune system react better and enhance the effects of the vaccine in treating breast cancer The vaccine consists of two irradiated allogeneic mammary carcinoma cell lines genetically modified to secrete human granulocyte-macrophage colony stimulating factor GM-CSF This open label single arm study is designed to recruit up to 40 subjects to identify 20 research subjects with HER-2neu-overexpressing Stage IV breast cancer eligible for study treatment
Detailed Description:
Breast cancer ranks second among cancer deaths in women In the year 2005 the American Cancer Society has estimated that 212240 new invasive cases of breast cancer will be diagnosed and predicts 40410 deaths will result from breast cancer While 80 of patients present with locoregional disease involving the breast andor axillary lymph nodes about half develop disseminated disease and ultimately die from it Stage IV breast cancer is typically managed with hormonal agents or conventional cytotoxic drugs Tumors quickly become resistant to these treatments Immunotherapy is a particularly attractive strategy for overcoming drug resistance and can be integrated with existing therapeutic modalities in an additive or synergistic fashion Immunotherapy is a type of treatment for cancer based on the idea that the immune system can be activated to destroy cancer cells that might be resistant to hormonal therapy and chemotherapy A vaccine is a kind of immunotherapy that delivers an antigen something that activates the immune system so that the immune system recognizes cells with that antigen as foreign and destroys any cells that display that antigen
The allogeneic breast tumor cell vaccine consists of two types of breast tumor cells developed from the tumor cells of patients with breast cancer The human granulocyte-macrophage colony-stimulating factor GM-CSF gene was used to genetically modify the breast tumor cells to secrete GM-CSF GM-CSF is a substance made by the body that helps the immune system recognize a tumor and destroy it The vaccine cells were irradiated to prevent them from growing or dividing The cells themselves are not radioactive The cells are stored frozen until the day of vaccination The total number of cells in each vaccine will be 500000000 divided into twelve injections given in the thighs and arms The choice of twelve injections for each vaccine is based on the volume of the vaccine and a finding that the body has a better chance to respond to the vaccine if it is injected into a number of different areas
We propose to test the safety and bioactivity of an allogeneic GM-CSF-secreting breast cancer vaccine when given in a specifically timed sequence with Cyclophosphamide and Trastuzumab two drugs commonly used to treat breast cancer In this study the Cyclophosphamide is used at lower doses than usual to help the vaccine to activate the patients immune system Trastuzumab will be given at doses that are commonly used to treat breast cancer and it may also increase the immune response The dose and scheduling of Cyclophosphamide and Trastuzumab used are based on testing the drugs with a GM-CSF-secreting vaccine in mice that get breast cancer and are the ones that enabled the vaccine to induce the most potent anti-tumor immunity The dose of vaccine cells is based on the safety of the same dose of a similar GM-CSF-secreting vaccine for pancreatic cancer This breast cancer vaccine has also been given to people with breast cancer by itself and with Cyclophosphamide and another chemotherapy drug Doxorubicin To date people have had no vaccine-related serious side effects but not enough people have received the vaccine to know if it treats breast cancer The vaccine is experimental and has not been approved by the US Food and Drug Administration FDA However the FDA has permitted its use in this research study This is the second study of this breast cancer vaccine and the first study to test this vaccine with Trastuzumab
The main purposes of this study are to test the safety clinical benefit and bioactivity of vaccine therapy in combination with Cyclophosphamide and Trastuzumab in patients with HER-2neu-overexpressing Stage IV breast cancer This study will also to test whether the Cyclophosphamide can eliminate the suppressive influence of regulatory T cells and whether Trastuzumab can increase antigen processing and presentation These drug activities may make the immune system react better and enhance the effects of the vaccine in treating breast cancer
The study is open to men and women with HER-2neu-overexpressing metastatic breast cancer Concurrent hormone therapy andor bisphosphonates standard breast cancer therapy that is not chemotherapy or other investigational therapy is allowed Patients may have received Trastuzumab in the past or continue on it while participating in this study About 40 people with HER-2neu positive breast cancer will enter in the study About 20 will pass the screening tests and receive the vaccine
Research subjects will receive a fixed dose of the allogeneic breast tumor vaccine consisting of two irradiated allogeneic breast cancer cell lines transfected with the GM-CSF gene in a specifically timed sequence with a low dose of Cyclophosphamide and Trastuzumab Patients will receive 300 mgm2 of Cyclophosphamide on day -1 and the vaccine on day 0 Weekly Trastuzumab will be timed to coincide with Cyclophosphamide administration Research subjects will receive three monthly vaccination cycles with a fourth and final boost vaccination cycle three months from the third cycle
Blood samples to measure GM-CSF levels will be taken on the day of vaccination every day for 4 days and then on day 7 after vaccination Blood samples to evaluate the safety of the vaccinations will be taken about once a week for one month following each vaccination During studies of the breast vaccine and similar vaccines in renal cell cancer prostate cancer pancreatic cancer and non-small cell lung cancer local symptoms of swelling and redness developed at the vaccine site between 2 and 7 days after vaccination In this study if the subjects vaccination site shows swelling over 1 cm in diameter a skin biopsy will be taken The skin biopsy will be evaluated to determine to what types of cells are important to the immune response Based on our previous preclinical and clinical data the biopsy will be taken on day 3 and possibly on day 7 after the first and third vaccinations Other tests and evaluations include history and physical examination vital signs CT of the chest abdomen and pelvis nuclear medicine bone scan pre-vaccination biopsy blood for immune monitoring and a skin test for delayed-type hypersensitivity DTH that is like a purified protein derivative PPD test and involves injecting pieces of a protein antigen HER-2neu that is delivered by the breast cancer vaccine The purpose of the DTH test is to evaluate whether the research subject has developed a systemic immune response to the breast cancer vaccine Tumor core needle biopsies will be obtained at baseline and on days 0 and 14 of vaccine cycle 1 only
Patients will be evaluated clinically and with laboratory testing for evidence of disease progression after each cycle or when otherwise clinically indicated Computed tomography CT scan of the chest abdomen and pelvis and nuclear medicine bone scan will also be performed to evaluate disease status prior to starting the study after vaccine cycle 3 and prior to and after vaccine cycle 4 About every three months cardiac function will be evaluated
The allogeneic breast tumor cell vaccine consists of two types of breast tumor cells developed from the tumor cells of patients with breast cancer The human granulocyte-macrophage colony-stimulating factor GM-CSF gene was used to genetically modify the breast tumor cells to secrete GM-CSF GM-CSF is a substance made by the body that helps the immune system recognize a tumor and destroy it The vaccine cells were irradiated to prevent them from growing or dividing The cells themselves are not radioactive The cells are stored frozen until the day of vaccination The total number of cells in each vaccine will be 500000000 divided into twelve injections given in the thighs and arms The choice of twelve injections for each vaccine is based on the volume of the vaccine and a finding that the body has a better chance to respond to the vaccine if it is injected into a number of different areas
We propose to test the safety and bioactivity of an allogeneic GM-CSF-secreting breast cancer vaccine when given in a specifically timed sequence with Cyclophosphamide and Trastuzumab two drugs commonly used to treat breast cancer In this study the Cyclophosphamide is used at lower doses than usual to help the vaccine to activate the patients immune system Trastuzumab will be given at doses that are commonly used to treat breast cancer and it may also increase the immune response The dose and scheduling of Cyclophosphamide and Trastuzumab used are based on testing the drugs with a GM-CSF-secreting vaccine in mice that get breast cancer and are the ones that enabled the vaccine to induce the most potent anti-tumor immunity The dose of vaccine cells is based on the safety of the same dose of a similar GM-CSF-secreting vaccine for pancreatic cancer This breast cancer vaccine has also been given to people with breast cancer by itself and with Cyclophosphamide and another chemotherapy drug Doxorubicin To date people have had no vaccine-related serious side effects but not enough people have received the vaccine to know if it treats breast cancer The vaccine is experimental and has not been approved by the US Food and Drug Administration FDA However the FDA has permitted its use in this research study This is the second study of this breast cancer vaccine and the first study to test this vaccine with Trastuzumab
The main purposes of this study are to test the safety clinical benefit and bioactivity of vaccine therapy in combination with Cyclophosphamide and Trastuzumab in patients with HER-2neu-overexpressing Stage IV breast cancer This study will also to test whether the Cyclophosphamide can eliminate the suppressive influence of regulatory T cells and whether Trastuzumab can increase antigen processing and presentation These drug activities may make the immune system react better and enhance the effects of the vaccine in treating breast cancer
The study is open to men and women with HER-2neu-overexpressing metastatic breast cancer Concurrent hormone therapy andor bisphosphonates standard breast cancer therapy that is not chemotherapy or other investigational therapy is allowed Patients may have received Trastuzumab in the past or continue on it while participating in this study About 40 people with HER-2neu positive breast cancer will enter in the study About 20 will pass the screening tests and receive the vaccine
Research subjects will receive a fixed dose of the allogeneic breast tumor vaccine consisting of two irradiated allogeneic breast cancer cell lines transfected with the GM-CSF gene in a specifically timed sequence with a low dose of Cyclophosphamide and Trastuzumab Patients will receive 300 mgm2 of Cyclophosphamide on day -1 and the vaccine on day 0 Weekly Trastuzumab will be timed to coincide with Cyclophosphamide administration Research subjects will receive three monthly vaccination cycles with a fourth and final boost vaccination cycle three months from the third cycle
Blood samples to measure GM-CSF levels will be taken on the day of vaccination every day for 4 days and then on day 7 after vaccination Blood samples to evaluate the safety of the vaccinations will be taken about once a week for one month following each vaccination During studies of the breast vaccine and similar vaccines in renal cell cancer prostate cancer pancreatic cancer and non-small cell lung cancer local symptoms of swelling and redness developed at the vaccine site between 2 and 7 days after vaccination In this study if the subjects vaccination site shows swelling over 1 cm in diameter a skin biopsy will be taken The skin biopsy will be evaluated to determine to what types of cells are important to the immune response Based on our previous preclinical and clinical data the biopsy will be taken on day 3 and possibly on day 7 after the first and third vaccinations Other tests and evaluations include history and physical examination vital signs CT of the chest abdomen and pelvis nuclear medicine bone scan pre-vaccination biopsy blood for immune monitoring and a skin test for delayed-type hypersensitivity DTH that is like a purified protein derivative PPD test and involves injecting pieces of a protein antigen HER-2neu that is delivered by the breast cancer vaccine The purpose of the DTH test is to evaluate whether the research subject has developed a systemic immune response to the breast cancer vaccine Tumor core needle biopsies will be obtained at baseline and on days 0 and 14 of vaccine cycle 1 only
Patients will be evaluated clinically and with laboratory testing for evidence of disease progression after each cycle or when otherwise clinically indicated Computed tomography CT scan of the chest abdomen and pelvis and nuclear medicine bone scan will also be performed to evaluate disease status prior to starting the study after vaccine cycle 3 and prior to and after vaccine cycle 4 About every three months cardiac function will be evaluated
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 |
|---|---|---|---|
| RAC 0605-778 | None | None | None |