Ignite Creation Date:
2025-12-25 @ 1:23 AM
Ignite Modification Date:
2025-12-25 @ 11:32 PM
Study NCT ID:
NCT00048893
Status:
TERMINATED
Last Update Posted:
2012-04-13
First Post:
2002-11-08
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Vaccine and Chemotherapy for Previously Untreated Metastatic Breast Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Multicenter Phase I-II Study of Tumor Vaccine Following Chemotherapy in Patients With Metastatic Breast Cancer Untreated With Chemo/Radiation 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 body's 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 (paclitaxel)/Cytoxan (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 body's 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 (paclitaxel)/Cytoxan (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 patient's 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 patient's 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:
True
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 03-C-0040 | None | None | View |