Intestinal Microbiota Impact for Prognosis and Treatment Outcomes in Early Luminal Breast Cancer and Pancreatic Cancer Patients

The gut microbiota (GM) can influence as effectiveness of immunotherapy as prognosis factor in cancer patients. The goal of the study to identify GM pattern is associated with poor and favourable treatment outcomes in breast cancer and pancreatic cancer patients for further treatment strategy proper planning.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Pancreas Cancer
• Intervention / Treatment: Drug: Doxorubicin; Drug: Cyclophosphamid; Drug: Paclitaxel; Drug: Carboplatin; Drug: mFOLFIRINOX

• Study Type: Observational
• Enrollment (Anticipated): 35

Contacts and Locations

Study Locations

• Russian Federation
  • Not Required
    • Moscow, Not Required, Russian Federation, Moscow
      • Recruiting
      • Moscow Clinical Scientific Center named after AS Loginov
      • Contact: Lyudmila Zhukova; Phone Number: 84953043035; Email: lyudmila.zhukova@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

• Early lum A and high risk lum B HER2- breast cancer
• Locally advanced resectable and/or borderline resectable panreatic cancer

Description

Inclusion Criteria:

• untreated early HR+ HER2- BC:

  1. planned neoadjuvant chemotherapy: dose dense doxorubicin and cyclophosphamide (AC) x 4 every 2 weeks followed by 12 weekly PAClitaxel + CARBOplatin every 21 days for 4 cycles
  2. TanyN1-3M0 Ki67>40% G3
  3. ECOG 0-1

• untreated early HR+ HER2- BC:

  1. TanyN0M0 Ki67<20% G1
  2. ECOG 0-1
  3. planned induction endocrine therapy (letrozole/anastrazole/tamoxifen)

• untreated locally-advanced and/or borderline resectable pancreas cancer:

  1. planned (neo)adjuvant chemotherapy: mFOLFIRINOX
  2. previous surgery ( only R0 resection) is allowed
  3. ECOG 0-1
  4. histology diagnosis verification
• Informed consent
• Eligible blood&fecal samples and tumor tissue for different time points

Exclusion Criteria:

• autoimmune disease
• active steroid therapy
• ECOG > 2
• any previous therapy for breast cancer
• metastatic cancer
• antibiotic use less than 28 days
• other tumor

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with luminal A breast cancer
Patients with high risk luminal B breast cancer	Drug: Doxorubicin; dose dense doxorubicin and cyclophosphamide (AC) x 4 every 2 weeks followed by 12 weekly PAClitaxel + CARBOplatin every 21 days for 4 cycles; Drug: Cyclophosphamid; dose dense doxorubicin and cyclophosphamide (AC) x 4 every 2 weeks followed by 12 weekly PAClitaxel + CARBOplatin every 21 days for 4 cycles; Drug: Paclitaxel; dose dense doxorubicin and cyclophosphamide (AC) x 4 every 2 weeks followed by 12 weekly PAClitaxel + CARBOplatin every 21 days for 4 cycles; Drug: Carboplatin; dose dense doxorubicin and cyclophosphamide (AC) x 4 every 2 weeks followed by 12 weekly PAClitaxel + CARBOplatin every 21 days for 4 cycles
Patients with high pancreatic cancer	Drug: mFOLFIRINOX; every 2 weeks: Oxaliplatin 65 mg/m2 IV over 3 hours on Day 1 Irinotecan 150 mg/m2 IV over 90 minutes on Day 1 Leucovorin(l-LV) 200 mg/m2 IV over 2 hours on Day 1 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal bacterial structure in BC and PnC (separately) patients with disease progression	Intestinal bacterial structure will performed by 16S RNA gene sequencing	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of ctDNA level in the each type of breast cancer patients from diagnosis till 24 months after completion neoadjuvant chemotherapy followed by surgery	Change from baseline of ctDNA level in the each type of breast cancer patients from diagnosis till 24 months after completion neoadjuvant chemotherapy followed by surgery	30 months (6 months treatment period+24 months follow up)
Change from baseline in intestinal bacterial structure in patients with early high risk luminal breast cancer of recurrence and increasing ctDNA level who are receiving neo/adjuvant chemotherapy regimens	Change from baseline in intestinal bacterial structure in patients with early high risk luminal breast cancer of recurrence and increasing ctDNA level who are receiving neo/adjuvant chemotherapy regimens. Intestinal bacterial structure will performed by 16S RNA gene sequencing.	30 months
Change from baseline in intestinal bacterial structure in PnC patients 12 months after after the completion of combined treatment	Intestinal bacterial structure will performed by 16S RNA gene sequencing	18 months (6 months treatment period+ 12 months follow up)
Change from baseline in intestinal bacterial structure in PnC patients with disease relapse on or after combined treatment completion (follow up 12 months)	Intestinal bacterial structure will performed by 16S RNA gene sequencing	18 months (6 months treatment period+ 12 months follow up)

Collaborators and Investigators

• Sponsor: Moscow Clinical Scientific Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 12, 2022
• Primary Completion (ANTICIPATED): May 12, 2025
• Study Completion (ANTICIPATED): August 1, 2025

Study Registration Dates

• First Submitted: June 21, 2022
• First Submitted That Met QC Criteria: October 12, 2022
• First Posted (ACTUAL): October 14, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 14, 2022
• Last Update Submitted That Met QC Criteria: October 12, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Breast Diseases; Pancreatic Diseases; Breast Neoplasms; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Carboplatin; Paclitaxel; Doxorubicin
• Other Study ID Numbers: Microbiome_BC&PnC

Drug and device information, study documents

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