Gut Microbiome & Gastrointestinal Toxicities as Determinants of Response to Neoadjuvant Chemo for Advanced Breast Cancer

• Sponsor: University of Arkansas (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02696759
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 61
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research is to test whether bacteria that normally live in the intestines play a role in fighting cancer. It is believed that the development and behavior of these immune cells may be influenced by bacteria and other microorganisms living in the gut. In turn, the activities of these immune cells could work with anti-cancer therapies to make them more, or less, effective.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Other: Blood & Fecal Collection	N/A

Detailed Description

Many chemotherapeutic agents compromise the integrity of the mucosal barrier in the gut, allowing translocation of gram-positive bacteria in secondary lymphoid organs. While this has, until recently, been considered an undesirable side-effect, it may also represent one mechanism by which chemotherapy stimulates an effective anti-cancer immune response. The purpose of this research is to test whether bacteria that normally live in the intestines play a role in fighting cancer. It is believed that the development and behavior of these immune cells may be influenced by bacteria and other microorganisms living in the gut. In turn, the activities of these immune cells could work with anti-cancer therapies to make them more, or less, effective. The hypothesis is that gut microbial composition can influence immune response to the tumor, resulting in inter-individual differences in the response to anti-cancer therapies.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Gut Microbiome and Gastrointestinal Toxicities as Determinants of the Response to Neoadjuvant Chemotherapies for Advanced Breast Cancer
• Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Aug 1, 2021
• Actual Study Completion Date: Aug 1, 2021

Arms and Interventions

Arm

Intervention/Treatment

Other: Blood & Fecal Collection Subjects receiving neoadjuvant chemotherapy for advanced breast cancer will be asked to complete questionnaires, provide two blood samples, and provide 2 fecal samples while receiving standard of care neoadjuvant chemotherapy

Other: Blood & Fecal Collection; Prior to first dose of chemotherapy: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package; (c) Questionnaire on health related quality of life. During chemotherapy: Questionnaires on health related quality of life and regarding any treatment side effects. Questionnaires will be completed every 2 weeks during standard office visits. After chemotherapy, prior to surgery: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Who Complete Fecal Collection [Through study completion, an average of 18 months]

   At least one fecal kit collected

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with invasive breast cancer and prescribed a regimen that includes neo-adjuvant therapy prior to breast surgery.

• Able to provide informed consent.

Exclusion Criteria:

• History of previous malignancy, other than non-melanoma skin cancers

• Inability to tolerate phlebotomy

• Immunosuppressive therapy for any other condition

• Fever or active uncontrolled infection in the last 4 weeks

• Inflammatory bowel disease

• Surgery of the stomach, small or large intestines, appendectomy, gastric bypass or gastric banding in the past 6 months.

• Active autoimmune disease, including, but not limited to, Systemic lupus erythematosus (SLE), Multiple sclerosis (MS), ankylosing spondylitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

• University of Arkansas

Investigators

• Principal Investigator: Issam Makhoul, MD, University of Arkansas

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 7, 2019

More Information

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT02696759
• Other Study ID Numbers: 204897
• First Posted: Mar 2, 2016
• Last Update Posted: Mar 16, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by University of Arkansas: Breast; Cancer
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Arm/Group Title	Blood & Fecal Collection
Arm/Group Description	Subjects receiving neoadjuvant chemotherapy for advanced breast cancer will be asked to complete questionnaires, provide two blood samples, and provide 2 fecal samples while receiving standard of care neoadjuvant chemotherapy Blood & Fecal Collection: Prior to first dose of chemotherapy: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package; (c) Questionnaire on health related quality of life. During chemotherapy: Questionnaires on health related quality of life and regarding any treatment side effects. Questionnaires will be completed every 2 weeks during standard office visits. After chemotherapy, prior to surgery: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package.
Period Title: Overall Study
STARTED	15
COMPLETED	15
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Blood & Fecal Collection
Arm/Group Description	Subjects receiving neoadjuvant chemotherapy for advanced breast cancer will be asked to complete questionnaires, provide two blood samples, and provide 2 fecal samples while receiving standard of care neoadjuvant chemotherapy Blood & Fecal Collection: Prior to first dose of chemotherapy: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package; (c) Questionnaire on health related quality of life. During chemotherapy: Questionnaires on health related quality of life and regarding any treatment side effects. Questionnaires will be completed every 2 weeks during standard office visits. After chemotherapy, prior to surgery: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 73.3%
>=65 years	4 26.7%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	15 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 40%
White	9 60%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Who Complete Fecal Collection
Description	At least one fecal kit collected
Time Frame	Through study completion, an average of 18 months

Outcome Measure Data

Analysis Population Description

Study was halted prematurely. Data analysis not complete.

Arm/Group Title	Blood & Fecal Collection
Arm/Group Description	Subjects receiving neoadjuvant chemotherapy for advanced breast cancer will be asked to complete questionnaires, provide two blood samples, and provide 2 fecal samples while receiving standard of care neoadjuvant chemotherapy Blood & Fecal Collection: Prior to first dose of chemotherapy: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package; (c) Questionnaire on health related quality of life. During chemotherapy: Questionnaires on health related quality of life and regarding any treatment side effects. Questionnaires will be completed every 2 weeks during standard office visits. After chemotherapy, prior to surgery: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package.
Measure Participants	10
Number [participants]	10 66.7%

Adverse Events

Time Frame	18 months
Arm/Group Title	Blood & Fecal Collection
Arm/Group Description	Subjects receiving neoadjuvant chemotherapy for advanced breast cancer will be asked to complete questionnaires, provide two blood samples, and provide 2 fecal samples while receiving standard of care neoadjuvant chemotherapy Blood & Fecal Collection: Prior to first dose of chemotherapy: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package; (c) Questionnaire on health related quality of life. During chemotherapy: Questionnaires on health related quality of life and regarding any treatment side effects. Questionnaires will be completed every 2 weeks during standard office visits. After chemotherapy, prior to surgery: (a) Blood sample for research; (b) Fecal sample for research using a kit provided by the research staff for home collection of the fecal sample. The kit may be brought back to the clinic or mailed in a discreet package.
All Cause Mortality
	Blood & Fecal Collection
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	Blood & Fecal Collection
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Blood & Fecal Collection
	Affected / at Risk (%)	# Events
Total	0/15 (0%)

Limitations/Caveats

The secondary objectives were removed because it was decided (due to a number of parameters including the departure of the PI and failure to meet the enrollment goal) that the samples would not be analyzed. Thus, the secondary objectives in the previous submissions are no longer relevant, and there are no results to report.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.