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RBX7455 Before Surgery for the Treatment of Operable Breast Cancer

Primary Purpose

Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Microbiota-based Formulation RBX7455
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anatomic Stage I Breast Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2

  • Histologically confirmed un-resected operable invasive adenocarcinoma of the breast >= 0.5cm

    • For cohort 1: Estrogen receptor (ER) and/or progesterone receptor (PR) positive >= 10%, and no human epidermal growth factor receptor 2 (HER2) amplification or overexpression
    • For cohort 2: Human epidermal growth factor receptor 2 (HER2) amplification with fluorescence in situ hybridization (FISH) ratio >= 2.0 or overexpression by immunohistochemistry 3+ with any ER and/or PR
    • For cohort 3: Triple negative. Estrogen receptor (ER) and/or progesterone receptor (PR) negative < 10%, and no human epidermal growth factor receptor 2 (HER2) amplification or overexpression
  • Patients must not receive neoadjuvant chemotherapy prior to surgery
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelet count >= 75,000/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Creatinine =< 2 x upper limit of normal (ULN)
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 x ULN
  • Albumin >= 3 g/dL
  • Willing and able to swallow capsules
  • Willing and able to complete the stool and serum testing required for the study
  • Willing to provide blood samples for correlative research purposes
  • Agrees not to take non-dietary probiotics through 8 weeks after receiving the course of study drug (including over-the counter [OTC] and prescription)
  • Agrees not to take any oral vancomycin, metronidazole, fidaxomicin, rifaximin, nitazoxanide, bezlotoxumab and intravenous immunoglobulin therapy (IVIG) through the 8-week follow-up assessment unless newly prescribed by a treating investigator during the course of the study

  • Willing to employ adequate contraception from the time of enrollment through 3 months after the final dose of RBX7455

    • Note: Adequate contraception methods include birth control pills, barrier device, intrauterine device
  • Capable of understanding the investigative nature, potential risks, and benefits of the study
  • Capable of providing valid informed consent
  • Willing to return to enrolling institution for all study visits (blood draws, etc)
  • Willing and able to complete the required Patient Medication Diary
  • Willing and able to meet all study requirements, including attending all assessment visits and telephone calls
  • Women of child bearing potential must have negative pregnancy test within 7 days of enrollment

Exclusion Criteria:

  • Requires systemic antibiotic therapy for other condition
  • Fecal microbiota transplant (FMT) within the past 6 months
  • FMT with an associated serious adverse event related to the FMT product or procedure
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimen

  • Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive or those on chronic steroids > 20 mg prednisone a day or prednisone-equivalent

    • Note: Must be off systemic steroids at least 90 days prior to enrollment. However, topical steroids, inhalants or steroid eye drops are permitted
  • Receiving any other investigational agent
  • History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis
  • Diagnosis of irritable bowel syndrome (IBS) as determined by Rome III criteria
  • History of chronic diarrhea
  • History of celiac disease
  • Currently has a colostomy
  • Intraabdominal surgery related to gastrointestinal tract within the last 60 days
  • Evidence of active, severe colitis
  • History of short gut syndrome or motility disorders
  • Requires the regular use of medications to manage bowel hypermotility
  • Active autoimmune disease that has required systemic treatment in the =< 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to randomization. Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded
  • Pregnancy
  • Breast feeding

Sites / Locations

  • Mayo Clinic in Florida

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (RBX7455)

Arm Description

Prior to standard of care surgery, patients receive RBX7455 orally (PO) 4 days a week for 2-4 weeks in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Incidence of adverse events
Assessed per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The maximum grade for each type of toxicity will be recorded for each patient, and frequency (percentage) of toxicity for all patients will be reported by study statistician and reviewed by primary disease site to determine toxicity patterns. Evaluation of RBX7455 will be assessed by physical exams and laboratory testing with number of patients with abnormal laboratory values and adverse events.

Secondary Outcome Measures

Systemic immunomodulatory effects
The percent change in plasma concentrations of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12, IL-13, IL-17A, IFN-gamma, TNF-alpha, CCL2 (MCP-1), CCL4 (MIP-1beta), granulocyte-colony stimulating factor (G-CSF), and granulocyte macrophage (GM)-CSF. will be summarized as mean (standard deviation) or median (range) where appropriate. Each of these factors will be plotted against time with the points belonging to a particular individual connected. Each graph will be visually inspected for trends across time and difference between treatment regimens. For each marker, the number of patients with at least a 2-fold increase/decrease in the number of cells/plasma concentration (marker specific response) after the first cycle of treatment as well as anytime during treatment will be determined.
Engraftment rate
Durability of bacterial engraftment of RBX7455
Will be evaluated with bacterial taxonomy using provided stool samples obtained by patient.

Full Information

First Posted
October 22, 2019
Last Updated
October 2, 2023
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT04139993
Brief Title
RBX7455 Before Surgery for the Treatment of Operable Breast Cancer
Official Title
A Pilot Trial of Preoperative Oral Microbiota-Based Investigational New Drug, RBX7455 to Target Immune Response in Patients With Operable Stage I-III Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
poor accrual
Study Start Date
August 31, 2020 (Actual)
Primary Completion Date
January 11, 2023 (Actual)
Study Completion Date
January 11, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This clinical trial studies the side effects and possible benefits of RBX7455 given before surgery in treating patients with breast cancer that can be removed by surgery (operable). RBX7455 contains live intestinal microbes (active drug), which are obtained from healthy human stool and may restore the normal balance of microorganisms in the intestines through the transplant of live and beneficial microorganisms.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the safety and tolerability of microbiota-based formulation RBX7455 (RBX7455) given for at least 2 weeks and not more than 4 weeks prior to surgery. II. To evaluate intratumoral immunomodulatory effects, including tumor infiltrating lymphocytes ( TILs), CD4, and CD8 T cells, in operable breast cancer patients. SECONDARY OBJECTIVES: I. To evaluate systemic immunomodulatory effects of RBX7455 by measuring circulating cytokines including IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12, IL-13, IL- 17A, IFN-gamma, TNF-alpha, CCL2 (MCP-1), CCL4 (MIP-1beta), granulocyte-colony stimulating factor (G-CSF), and granulocyte macrophage (GM)-CSF before and after treatment with RBX7455. II. To assess stool microbiome α-diversity, bacterial abundance, and bacterial taxonomy before and after treatment with RBX7455. III. To assess the durability of bacterial engraftment of RBX7455 in the stool at 8 weeks and 6 months. OUTLINE: Prior to standard of care surgery, patients receive RBX7455 orally (PO) 4 days a week for 2-4 weeks in the absence of disease progression or unacceptable toxicity. After completion of surgery, patients are followed up at 8 weeks and 6 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Breast Adenocarcinoma, Invasive Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8, Triple-Negative Breast Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (RBX7455)
Arm Type
Experimental
Arm Description
Prior to standard of care surgery, patients receive RBX7455 orally (PO) 4 days a week for 2-4 weeks in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Microbiota-based Formulation RBX7455
Other Intervention Name(s)
RBX 7455, RBX-7455, RBX7455
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
Assessed per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The maximum grade for each type of toxicity will be recorded for each patient, and frequency (percentage) of toxicity for all patients will be reported by study statistician and reviewed by primary disease site to determine toxicity patterns. Evaluation of RBX7455 will be assessed by physical exams and laboratory testing with number of patients with abnormal laboratory values and adverse events.
Time Frame
Up to 4 weeks prior to surgery
Secondary Outcome Measure Information:
Title
Systemic immunomodulatory effects
Description
The percent change in plasma concentrations of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12, IL-13, IL-17A, IFN-gamma, TNF-alpha, CCL2 (MCP-1), CCL4 (MIP-1beta), granulocyte-colony stimulating factor (G-CSF), and granulocyte macrophage (GM)-CSF. will be summarized as mean (standard deviation) or median (range) where appropriate. Each of these factors will be plotted against time with the points belonging to a particular individual connected. Each graph will be visually inspected for trends across time and difference between treatment regimens. For each marker, the number of patients with at least a 2-fold increase/decrease in the number of cells/plasma concentration (marker specific response) after the first cycle of treatment as well as anytime during treatment will be determined.
Time Frame
Up t0 6 months after treatment
Title
Engraftment rate
Time Frame
Up to 6 months after treatment
Title
Durability of bacterial engraftment of RBX7455
Description
Will be evaluated with bacterial taxonomy using provided stool samples obtained by patient.
Time Frame
Up to 6 months after treatment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Histologically confirmed un-resected operable invasive adenocarcinoma of the breast >= 0.5cm For cohort 1: Estrogen receptor (ER) and/or progesterone receptor (PR) positive >= 10%, and no human epidermal growth factor receptor 2 (HER2) amplification or overexpression For cohort 2: Human epidermal growth factor receptor 2 (HER2) amplification with fluorescence in situ hybridization (FISH) ratio >= 2.0 or overexpression by immunohistochemistry 3+ with any ER and/or PR For cohort 3: Triple negative. Estrogen receptor (ER) and/or progesterone receptor (PR) negative < 10%, and no human epidermal growth factor receptor 2 (HER2) amplification or overexpression Patients must not receive neoadjuvant chemotherapy prior to surgery Absolute neutrophil count (ANC) >= 1000/mm^3 Platelet count >= 75,000/mm^3 Hemoglobin >= 9.0 g/dL Creatinine =< 2 x upper limit of normal (ULN) Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 x ULN Albumin >= 3 g/dL Willing and able to swallow capsules Willing and able to complete the stool and serum testing required for the study Willing to provide blood samples for correlative research purposes Agrees not to take non-dietary probiotics through 8 weeks after receiving the course of study drug (including over-the counter [OTC] and prescription) Agrees not to take any oral vancomycin, metronidazole, fidaxomicin, rifaximin, nitazoxanide, bezlotoxumab and intravenous immunoglobulin therapy (IVIG) through the 8-week follow-up assessment unless newly prescribed by a treating investigator during the course of the study Willing to employ adequate contraception from the time of enrollment through 3 months after the final dose of RBX7455 Note: Adequate contraception methods include birth control pills, barrier device, intrauterine device Capable of understanding the investigative nature, potential risks, and benefits of the study Capable of providing valid informed consent Willing to return to enrolling institution for all study visits (blood draws, etc) Willing and able to complete the required Patient Medication Diary Willing and able to meet all study requirements, including attending all assessment visits and telephone calls Women of child bearing potential must have negative pregnancy test within 7 days of enrollment Exclusion Criteria: Requires systemic antibiotic therapy for other condition Fecal microbiota transplant (FMT) within the past 6 months FMT with an associated serious adverse event related to the FMT product or procedure Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimen Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive or those on chronic steroids > 20 mg prednisone a day or prednisone-equivalent Note: Must be off systemic steroids at least 90 days prior to enrollment. However, topical steroids, inhalants or steroid eye drops are permitted Receiving any other investigational agent History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis Diagnosis of irritable bowel syndrome (IBS) as determined by Rome III criteria History of chronic diarrhea History of celiac disease Currently has a colostomy Intraabdominal surgery related to gastrointestinal tract within the last 60 days Evidence of active, severe colitis History of short gut syndrome or motility disorders Requires the regular use of medications to manage bowel hypermotility Active autoimmune disease that has required systemic treatment in the =< 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to randomization. Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded Pregnancy Breast feeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria I Vazquez Roque
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States

12. IPD Sharing Statement

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RBX7455 Before Surgery for the Treatment of Operable Breast Cancer

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