Ignite Creation Date:
2024-05-05 @ 11:27 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00048893
Status:
TERMINATED
Last Update Posted:
2012-04-13
First Post:
2002-11-08
Brief Title:
Vaccine and Chemotherapy for Previously Untreated Metastatic Breast Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Multicenter Phase I-II Study of Tumor Vaccine Following Chemotherapy in Patients With Metastatic Breast Cancer Untreated With ChemoRadiation in the Previous 18 Months Vaccine-Induced Bias of T-Cell Repertoire Reconstitution After T-Cell Re-Infusion
Status:
TERMINATED
Status Verified Date:
2012-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The study was closed to accrual due to very poor enrollment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the effectiveness of chemotherapy and a combination of vaccines to treat metastatic breast cancer breast cancer that has spread beyond the breast in patients whose cancer cells have a protein called carcinoembryonic antigen CEA on their surface Patients who require surgery or radiation therapy or both will receive these treatments as well
Patients 18 years of age and older with previously untreated metastatic breast cancer may be eligible for this study Newly diagnosed patients may not have received prior chemotherapy Patients previously diagnosed with local disease may have received chemotherapy or radiation therapy at least 18 months before entering the current study Patients may have received hormonal therapy for stage IV disease Candidates are screened with a medical history and physical examination blood and urine tests x-rays heart and lung tests and a test to determine the presence of CEA on their tumor cells
Participants undergo the following procedures
1 Central venous line Under local or general anesthesia an intravenous catheter plastic tube is inserted into a major vein in the chest It is used to give chemotherapy and other medications and to withdraw blood samples
2 Apheresis Before beginning treatment and at various times before and after chemotherapy patients undergo apheresis to collect white blood cells for later re-infusion at the time of immunizations and to evaluate the bodys response to the vaccines For this procedure blood is collected through the central venous catheter and circulated through a machine that separates the white cells from the rest of the blood The white cells are removed and frozen for later use The rest of the blood is returned to the patient through the catheter
3 First vaccine Before starting chemotherapy patients receive one subcutaneous under the skin injection of a vaccine called rV-CEA-Tricom along with subcutaneous injections of granulocyte macrophage colony stimulating factor GM-CSF Sargramostim a drug that stimulates the bone marrow to release white blood cells and white cell precursors into the bloodstream
4 Chemotherapy
Taxol paclitaxelCytoxan cyclophosphamide Patients receive three to five cycles of Taxol and Cytoxan Taxol is given as a continuous 72-hour intravenous intravenous IV through a vein infusion and Cytoxan is given daily for 3 days intravenously over 1 hour Cycles are 21 to 42 usually 28 days After each cycle patients also receive growth colony stimulating factor G-CSF a drug that helps boost white cells
Patients 18 years of age and older with previously untreated metastatic breast cancer may be eligible for this study Newly diagnosed patients may not have received prior chemotherapy Patients previously diagnosed with local disease may have received chemotherapy or radiation therapy at least 18 months before entering the current study Patients may have received hormonal therapy for stage IV disease Candidates are screened with a medical history and physical examination blood and urine tests x-rays heart and lung tests and a test to determine the presence of CEA on their tumor cells
Participants undergo the following procedures
1 Central venous line Under local or general anesthesia an intravenous catheter plastic tube is inserted into a major vein in the chest It is used to give chemotherapy and other medications and to withdraw blood samples
2 Apheresis Before beginning treatment and at various times before and after chemotherapy patients undergo apheresis to collect white blood cells for later re-infusion at the time of immunizations and to evaluate the bodys response to the vaccines For this procedure blood is collected through the central venous catheter and circulated through a machine that separates the white cells from the rest of the blood The white cells are removed and frozen for later use The rest of the blood is returned to the patient through the catheter
3 First vaccine Before starting chemotherapy patients receive one subcutaneous under the skin injection of a vaccine called rV-CEA-Tricom along with subcutaneous injections of granulocyte macrophage colony stimulating factor GM-CSF Sargramostim a drug that stimulates the bone marrow to release white blood cells and white cell precursors into the bloodstream
4 Chemotherapy
Taxol paclitaxelCytoxan cyclophosphamide Patients receive three to five cycles of Taxol and Cytoxan Taxol is given as a continuous 72-hour intravenous intravenous IV through a vein infusion and Cytoxan is given daily for 3 days intravenously over 1 hour Cycles are 21 to 42 usually 28 days After each cycle patients also receive growth colony stimulating factor G-CSF a drug that helps boost white cells
Detailed Description:
BACKGROUND Metastatic breast cancer remains to this day a mostly incurable disease with less than 10 of patients reaching a long-term disease free survival This study proposes using an immune-depleting chemotherapy as platform for immunotherapy It is based on the following hypotheses and understanding
The combination of dose-intensive followed by immune-depleting chemotherapy provides a platform for subsequent immunotherapy by
1 Lengthening the progression-free survival period thus allowing time for a slow acting therapy such as vaccination to be effective
2 Maximally decreasing the patients tumor burden This has been shown both in clinical and experimental settings to be desirable if not necessary for immunotherapy to be effective
3 Decreasing the tumor burden which may also decrease a tumor-induced immuno-suppressive effect linked to tumor bulk
4 Providing tumor antigen exposure following immune depletion in the form of repeated immunizations This may take advantage of the pattern of immune reconstitution following immune depleting therapy at early time points antigen-driven peripheral expansion of T-cells and the renewal of a T-cell repertoire biased towards tumor antigens and anti-tumor responses at later time points
Low antigenicity of tumor antigens and immune tolerance may be overcome in a clinically relevant fashion by providing exposure to the tumor antigens the carcino-embryonic antigen CEA in a more immunogenic presentation along with added co-stimulatory signal in the form of two poxvirus-based recombinant vaccines
Due to the post immune depletion defects and delay in immune reconstitution an adequate immune response to vaccines may not occur unless the patients are provided following immune depletion with unaltered T-cells in the form of re-infusion of pre-chemotherapy lymphocytes
The late recovery of thymic function 18 to 24 months with reappearance of naive T-cells may play a determinant role in the prevention of later disease progression It is the rationale for a late series of immunizations
ELIGIBILITY Patients with metastatic breast cancer untreated with chemotherapy or radiation in the previous 18 months with CEA positivity in either the tumor or the serum
OBJECTIVES The primary objectives are to evaluate biologically this immunization strategy by assessing CEA specific T-cell responses as well as clinically by comparing the patient event free survival EFS to our historical control protocol 96-C-0104 in which patients have received the same conventional therapy but no immunization
DESIGN Before any chemotherapy patients will be immunized with one of two tumor-specific recombinant poxvirus-based deoxyribonucleic acid DNA Tricom vaccines and sensitized lymphocytes will be cryopreserved Patients will then receive conventional induction therapy with Paclitaxel Cyclophosphamide and Doxorubicin surgery and or radiation as indicated for local control then immune depleting chemotherapy with Fludarabine Cyclophosphamide Following immune depletion patients will receive 9 immunization boosts over the next 30 months Patients whose disease progress through the vaccination schedule may under certain circumstances receive further vaccinations under a more intensive schedule monthly
The combination of dose-intensive followed by immune-depleting chemotherapy provides a platform for subsequent immunotherapy by
1 Lengthening the progression-free survival period thus allowing time for a slow acting therapy such as vaccination to be effective
2 Maximally decreasing the patients tumor burden This has been shown both in clinical and experimental settings to be desirable if not necessary for immunotherapy to be effective
3 Decreasing the tumor burden which may also decrease a tumor-induced immuno-suppressive effect linked to tumor bulk
4 Providing tumor antigen exposure following immune depletion in the form of repeated immunizations This may take advantage of the pattern of immune reconstitution following immune depleting therapy at early time points antigen-driven peripheral expansion of T-cells and the renewal of a T-cell repertoire biased towards tumor antigens and anti-tumor responses at later time points
Low antigenicity of tumor antigens and immune tolerance may be overcome in a clinically relevant fashion by providing exposure to the tumor antigens the carcino-embryonic antigen CEA in a more immunogenic presentation along with added co-stimulatory signal in the form of two poxvirus-based recombinant vaccines
Due to the post immune depletion defects and delay in immune reconstitution an adequate immune response to vaccines may not occur unless the patients are provided following immune depletion with unaltered T-cells in the form of re-infusion of pre-chemotherapy lymphocytes
The late recovery of thymic function 18 to 24 months with reappearance of naive T-cells may play a determinant role in the prevention of later disease progression It is the rationale for a late series of immunizations
ELIGIBILITY Patients with metastatic breast cancer untreated with chemotherapy or radiation in the previous 18 months with CEA positivity in either the tumor or the serum
OBJECTIVES The primary objectives are to evaluate biologically this immunization strategy by assessing CEA specific T-cell responses as well as clinically by comparing the patient event free survival EFS to our historical control protocol 96-C-0104 in which patients have received the same conventional therapy but no immunization
DESIGN Before any chemotherapy patients will be immunized with one of two tumor-specific recombinant poxvirus-based deoxyribonucleic acid DNA Tricom vaccines and sensitized lymphocytes will be cryopreserved Patients will then receive conventional induction therapy with Paclitaxel Cyclophosphamide and Doxorubicin surgery and or radiation as indicated for local control then immune depleting chemotherapy with Fludarabine Cyclophosphamide Following immune depletion patients will receive 9 immunization boosts over the next 30 months Patients whose disease progress through the vaccination schedule may under certain circumstances receive further vaccinations under a more intensive schedule monthly
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 |
|---|---|---|---|
| 03-C-0040 | None | None | None |