Clinical Study of Personalized Chemotherapy for Breast Cancer With Low Doses of Cyclophosphamide

Clinical Study of Personalized Chemotherapy for Breast Cancer With Low Doses of Cyclophosphamide, Taking Into Account the Reparative Cycle of Tumor Cells

The goal of this study is to evaluate the safety and clinical efficacy of personalized chemotherapy with low doses of cyclophosphamide administered taking into account the reparative cycle of tumor cells in participants with breast cancer (stage IV or disease progression). The main question it aims to answer is: Does personalized chemotherapy of breast cancer with low doses of cyclophosphamide, taking into account the reparative cycle of tumor cells, lead to a significant reduction in tumor size and improvement in the visual status of controlled tumor foci relative to their initial state? During the preparatory stage, a tumor sample from participant is harvested intraoperatively. The primary culture is obtained from this tumor tissue sample. Repair cycle time is estimated, and the day when tumor cells are synchronized at the cell cycle G2/M phase is identified. The schedule of administering cyclophosphamide and DNAmix complex composite preparation is calculated according to the resulting time points. According to the elaborated regimen, the participant receives 4 intravenous cyclophosphamide injections at the dose of 300 mg/m2 in combination with 4 injections of 1-12 mg of DNAmix administered into prominent tumor nidi and lymph depots. The participant receives from 2 to 6 courses of therapy. The interval between courses is 21 days.

Study Overview

• Status: Recruiting
• Conditions: Stage IV Breast Cancer
• Intervention / Treatment: Combination product: Karanahan

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Anastasia Proskurina; Phone Number: +7-913-715-6920; Email: labmolbiol@mail.ru

Study Locations

• Russian Federation
  • Novosibirsk Region
    • Novosibirsk, Novosibirsk Region, Russian Federation, 630090
      • Recruiting
      • Karanahan Llc
      • Contact: Anastasia Proskurina; Email: labmolbiol@mail.ru
      • Principal Investigator: Sergey Sidorov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• stage IV breast cancer or progression of the disease with the presence of foci accessible for biopsy of tumor material;
• complete awareness of the patient about the prognosis of the disease and the proposed treatment;
• the volume of tumor material required for vital assessment of the time parameters of the individual reparative cycle of tumor cells must be at least 4 cm3;
• tumor cells transferred to primary culture must be in a state of proliferative activity.

Exclusion Criteria:

• severe decompensated cardiovascular, respiratory, hepatic, renal failure;
• presence of an acute infectious disease;
• intolerance to cyclophosphamide;
• severe neutropenia - the content of neutrophils is less than 1000 per 1 μl of blood;
• simultaneous participation in another clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Karanahan; Reparative cycle of tumor cells is assessed at the preliminary stage in in vitro culture. According to the elaborated regimen, the patient receives 4 intravenous cyclophosphamide injections at the dose of 300 mg/m2 in combination with 4 injections of 1-12 mg of DNAmix administered into prominent tumor nidi and lymph depots. The participant receives from 2 to 6 courses of therapy. The interval between courses is 21 days.

Combination product: Karanahan; During the preparatory stage, a tumor sample from participant is harvested intraoperatively. The primary culture is obtained from this tumor tissue sample. Repair cycle time is estimated, and the day when tumor cells are synchronized at the cell cycle G2/M phase is identified. The schedule of administering cyclophosphamide and DNAmix complex composite preparation is calculated according to the resulting time points. According to the elaborated regimen, the participant receives 4 intravenous cyclophosphamide injections at the dose of 300 mg/m2 in combination with 4 injections of 1-12 mg of DNAmix administered into prominent tumor nidi and lymph depots. The participant receives from 2 to 6 courses of therapy. The interval between courses is 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The size of tumor foci	Estimation of the size and visual condition of controlled tumor foci relative to their initial state. Tumor response assessment using the Response Evaluation Criteria In Solid Tumors (RECIST 1.1).	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The quality of life score	Changes in participants' quality of life during the therapy (score) according to the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30, version 3.0). The scale ranges in score from 0 to 100. Higher score means higher quality of life.	2 months
The immunomodulatory effect	The number of CD4+CD25+FoxP3+ regulatory T cells and CD8+CD107a+ T cells is mesuared in participants' blood before therapy and after 2 months using corresponding antibodies. Increase in number of these cells by 14% or more means the development of the adaptive antitumor immune response.	2 months

Collaborators and Investigators

• Sponsor: KARANAHAN

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: Karanahan

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No