Proteome-based Immunotherapy of Brain Metastases From Breast Cancer

NCT01782274 | Unknown Phase 2 DMC

• 1 other identifier: BrCr/2012
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neoplasm Metastasis

Keywords

Neoplasm Metastasis; Brain metastasis; Breast cancer

Outcome Measures

Primary Outcomes (1)

• All cause mortality

  2 years

Secondary Outcomes (1)

• Complete disappearance of all tumor foci

  2 years

Other Outcomes (1)

• reduction of tumor size by no less than 50% and absence of new foci

  2 years

Study Arms (2)

allogeneic stem cells

EXPERIMENTAL

3 ml suspension of allogeneic hematopoietic 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.

Biological: Dendritic vaccine, allogeneic hematopoietic stem cells, cytotoxic lymphocytes

autologous stem cells

ACTIVE COMPARATOR

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. 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.

Biological: Dendritic vaccine, autologous hematopoietic stem cells, cytotoxic lymphocytes

Interventions

Dendritic vaccine, allogeneic hematopoietic stem cells, cytotoxic lymphocytes BIOLOGICAL

allogeneic stem cells

Dendritic vaccine, autologous hematopoietic stem cells, cytotoxic lymphocytes BIOLOGICAL

autologous stem cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• NeuroVita Clinic: lead
• Blokhin's Russian Cancer Research Center: collaborator
• Russian Foundation of Technological Development: collaborator
• The Serbsky State Scientific Center for Social and Forensic Psychiatry: collaborator
• National Institute of Regenerative Medicine: collaborator
• SRC Bioclinicum: collaborator

Study Sites (1)

ZAO "NeuroVita Clinic of Interventional and Restorative Neurology and Therapy"

Moscow, 115478, Russia

Location

Related Publications (2)

• Bryukhovetskiy IS, Mischenko PV, Tolok EV, Zaitcev SV, Khotimchenko YS, Bryukhovetskiy AS. Directional migration of adult hematopoeitic progenitors to C6 glioma in vitro. Oncol Lett. 2015 Apr;9(4):1839-1844. doi: 10.3892/ol.2015.2952. Epub 2015 Feb 10.

  PMID: 25789053 RESULT

• Bryukhovetskiy A, Shevchenko V, Kovalev S, Chekhonin V, Baklaushev V, Bryukhovetskiy I, Zhukova M. To the novel paradigm of proteome-based cell therapy of tumors: through comparative proteome mapping of tumor stem cells and tissue-specific stem cells of humans. Cell Transplant. 2014;23 Suppl 1:S151-70. doi: 10.3727/096368914X684907. Epub 2014 Oct 9.

  PMID: 25303679 RESULT

MeSH Terms

Conditions

Neoplasm Metastasis; Brain Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Andrey S. Bryukhovetskiy, MD

  ZAO "NeuroVita Clinic of Interventional and Restorative Neurology and Therapy"

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2013
• First Posted: February 1, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2020
• Last Updated: October 12, 2017

Record last verified: 2017-10

Locations

RU (1)