Proteome-based Immunotherapy of Brain Metastases From Breast Cancer
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Purpose
Trial Hypothesis: Acute, progressing lethal neurooncological process can be transferred into chronic and non-lethal, the survival rates and life quality can be improved by of control of tumor cells (TCs) quantity and targeted regulation of effector functions of tumor stem cells (TSCs).
Brief Description:
The first line therapy of brain metastases of breast cancer (BMBC) involves allogeneic haploidentical hematopoietic stem cells (HSCs), dendritic vaccine (DV) and cytotoxic lymphocytes (CTLs).
TCs and TSCs are isolated from BMBC sample. Dendritic cells are isolated from peripheral blood mononuclear cells and cultured. Tumor sample provides tumor specific antigens to prepare DV. CTLs are obtained from peripheral blood after DV administrations. HSCs are harvested from closely related donor after granulocyte-colony-stimulating factor (G-CSF) administration.
Allogeneic HSCs are administered intrathecally 5 times every 2 weeks, at day 1, 14, 28, 42, 56. DV is given 3 times every 2 weeks (day 14, 28, 42) subcutaneously in four points. CTLs are administered every 2 weeks for 3 months, then 3 times every 1 month intrathecally. Six months after the therapy completion, the efficiency is evaluated and the cohort demonstrating efficiency continues the therapy, while cohort demonstrating no efficiency is transferred to active comparator arm.
Second line therapy involves DV with recombinant proteins, CTLs and autologous HSC with modified proteome. Autologous HSCs are mobilized by G-CSF.
Carcinogenesis-free intracellular pathways of signal transduction able to respond to targeted regulation of therapeutic cell systems with specific properties, are detected in TSCs using complete transcriptome profiling of gene expression, proteome mapping and profiling of proteins, bioinformation and mathematical analysis and mathematical modeling of protein profiles. To find key oncospecific proteins in TSCs and TCs, the targets for TSCs regulation are detected, as well as protein ligands able to regulate reproductive and proliferative properties of TSCs.
Using these data of TCs and TSCs proteins, the cell preparations to initiate adoptive immune response are prepared: DV loaded with recombinant proteins analogous to key tumor antigens, CTLs and autologous proteome-based HSCs.
Autologous HSCs, DV and CTLs are administered as in the first line therapy.
| Condition | Intervention | Phase |
|---|---|---|
|
Neoplasm Metastasis |
Biological: Dendritic vaccine, allogeneic hematopoietic stem cells, cytotoxic lymphocytes Biological: Dendritic vaccine, autologous hematopoietic stem cells, cytotoxic lymphocytes |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Proteome-based Personalized Immunotherapy of Brain Metastases From Breast Cancer |
- All cause mortality [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Complete disappearance of all tumor foci [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- reduction of tumor size by no less than 50% and absence of new foci [ Time Frame: 2 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 60 |
| Study Start Date: | December 2012 |
| Estimated Study Completion Date: | December 2017 |
| Estimated Primary Completion Date: | December 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: allogeneic stem cells |
Biological: Dendritic vaccine, allogeneic hematopoietic stem cells, cytotoxic lymphocytes
3 ml suspension of allogeneic hematopoietic stem cells in 0.9%NaCl solution is administered in L3-L4 vertebrae interspace with 16-18G needle. The preparation is administered every 2 weeks for the first 2 months (at day 1, 14, 28, 42, 56). 2 ml of individual dendritic vaccine are administered subcutaneously in 4 points (shoulders and abdomen) 3 times every 14 days from the therapy beginning (at day 14, 28 and 42). Meloxicam, 7.5mcg once a day is started from day 7 till day 42. Preparation of cytotoxic lymphocytes is administered intrathecally once in 2 weeks during the first 3 months, and then once in a month for three months.
|
| Active Comparator: autologous stem cells |
Biological: Dendritic vaccine, autologous hematopoietic stem cells, cytotoxic lymphocytes
3 ml suspension of proteome-modified autologous hematopoietic cells in 0.9%NaCl solution is administered in L3-L4 vertebrae interspace with 16-18G needle every 2 weeks for the first 2 months (at day 1, 14, 28, 42, 56). 2 ml of individual dendritic vaccine are administered subcutaneously in 4 points (shoulders and abdomen) 3 times every 14 days from the therapy beginning (at day 14, 28 and 42). Meloxicam, 7.5mcg once a day is started from day 7 till day 42. Preparation of cytotoxic lymphocytes is administered intrathecally once in 2 weeks for the first 3 months, and then once in a month for three months.
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Morphologically confirmed breast cancer metastases to brain (in case of relapse and impossibility of biopsy, diagnosis based on radiological and other diagnostic methods)
- Brain metastases of breast cancer refractor to the 1-st and following conventional chemotherapies and radiotherapy, in case their removal is not possible
- Brain metastases of breast cancer relapses after no less than one course of conventional chemotherapy and radiotherapy in case their removal is not possible.
- Availability of HLA partially compatible related donor
- Life expectancy of no less than 3 months
- Absence of severe decompensated organ dysfunction
- Informed consent of the patient
- Informed consent of the donor
Exclusion Criteria:
- Failure to meet one of the inclusion criteria
Contacts and Locations| Russian Federation | |
| ZAO "NeuroVita Clinic of Interventional and Restorative Neurology and Therapy" | |
| Moscow, Russian Federation, 115478 | |
| Principal Investigator: | Andrey S. Bryukhovetskiy, MD | ZAO "NeuroVita Clinic of Interventional and Restorative Neurology and Therapy" |
More Information
No publications provided
| Responsible Party: | NeuroVita Clinic |
| ClinicalTrials.gov Identifier: | NCT01782274 History of Changes |
| Other Study ID Numbers: | BrCr/2012 |
| Study First Received: | January 30, 2013 |
| Last Updated: | January 30, 2013 |
| Health Authority: | Russia: Ethics Committee of FGBU "Federal Research Center for Specialized Types of Medical Care and Medical Technologies" of FMBA Russia: Scientific Board of FGBU "Federal Research Center for Specialized Types of Medical Care and Medical Technologies" of FMBA Russia: Ethics Committee of FGBU N.N. Blokhin Russian Cancer Research Centre of RAMN Russia: Scientific Board of FGBU N.N. Blokhin Russian Cancer Research Centre of RAMN |
Keywords provided by NeuroVita Clinic:
|
Neoplasm Metastasis Brain metastasis Breast cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms Neoplasm Metastasis Neoplasms, Second Primary Brain Neoplasms Neoplasms by Site Breast Diseases Skin Diseases |
Neoplastic Processes Pathologic Processes Central Nervous System Neoplasms Nervous System Neoplasms Brain Diseases Central Nervous System Diseases Nervous System Diseases |
ClinicalTrials.gov processed this record on May 16, 2013