Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
Conditions
Interventions
Intervention1: Fecal microbiota transplantation: Fecal microbiota transplantation will be prepared from stool donated by rigorously screened exceptional responders with triple-negative breast cancer w
Sponsors
Josh Thomas Georgy
Christian Medical College Vellore
Eligibility
Inclusion criteria
Inclusion criteria: Recipient inclusion criteria 1. Adults aged 18 years or older with a diagnosis of triple-negative breast cancer. 2. Demonstrable residual invasive disease after four of eight planned cycles of neoadjuvant chemoimmunotherapy, confirmed by image-guided core biopsy. 3. Able to provide written informed consent and understand the infectious risks associated with fecal microbiota transplantation. 4. Scheduled to receive fecal microbiota transplantation as part of the study protocol. 5. Understand that data regarding the long-term safety of fecal microbiota transplantation in this setting are limited. 6. Eastern Cooperative Oncology Group performance status from zero to two, corresponding to a Karnofsky performance status of at least 60 percent. 7. Cardiac function with left ventricular ejection fraction at rest of at least 40 percent or shortening fraction greater than 25 percent. 8. Total bilirubin no more than 2.5 milligrams per decilitre, except in participants with Gilbert syndrome or haemolysis. 9. Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase less than five times the institutional upper limit of normal. 10. Serum creatinine within the institutional normal range or, if outside the normal range, measured or estimated creatinine clearance or glomerular filtration rate of at least 40 millilitres per minute per 1.73 square metres. 11. DLCO corrected for Hb, FEV1 and forced vital capacity of at least 50 percent predicted. 12. Women of child-bearing potential and men must agree to use adequate contraception before study entry and throughout study participation. Donor eligibility Adults aged 18 years or older from the approved donor cohort who achieved pathologic complete response after completing eight cycles of neoadjuvant chemoimmunotherapy, provide written consent for stool donation, and pass the protocol-defined comprehensive donor screening.
Exclusion criteria
Exclusion criteria: Recipient exclusion criteria 1. History of inflammatory bowel disease, which is an absolute contraindication, or another significant gastrointestinal disorder including coeliac disease, malabsorption or colorectal carcinoma. 2. Immunodeficiency, including human immunodeficiency virus infection or previous transplantation. 3. Active hepatitis B or hepatitis C infection. 4. Current systemic corticosteroid therapy exceeding prednisone 10 milligrams daily or equivalent, or treatment with other immunosuppressive agents. 5. Use of systemic antibiotics or probiotics within two weeks before fecal microbiota transplantation. 6. Known allergy to any component of the fecal microbiota transplantation preparation or severe dietary allergy, including peanut or seafood allergy. 7. Pregnancy or breastfeeding. 8. Concurrent enrolment in another interventional clinical trial. 9. Previous allogeneic haematopoietic stem-cell transplantation. 10. Delayed gastric emptying syndrome, large hiatal hernia, chronic aspiration, significant allergies to foods not excluded from the donor diet, end-stage liver disease, acute active gastrointestinal infection including typhlitis, diverticulitis or appendicitis, or previous total colectomy. 11. Human immunodeficiency virus-positive status. 12. Unable to receive a retention enema or undergo backup colonoscopy-guided administration. Donor exclusion: Any clinically significant gastrointestinal or liver disorder, previous major intestinal surgery, malignancy other than the treated breast cancer, recent antibiotic use or hospitalization, significant psychiatric illness or alcohol use, or any positive protocol-defined blood, urine or stool test for transmissible infection, enteric pathogen, parasite, viral infection or multidrug-resistant organism.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and feasibility of faecal microbiota transplantation during the safety lead-in and the proportion of participants achieving pathologic complete response, defined as no residual invasive carcinoma in the breast or sampled regional lymph nodes, corresponding to ypT0 or ypTis and ypN0.Timepoint: Safety assessed 4 weeks after the administration of FMT. PCR assessed at 10-12 weeks at time of breast surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Successful donor microbiome engraftment, defined as detection of donor-specific bacterial strains & a shift in recipient beta diversity toward the donor microbiome profile.Timepoint: At baseline & at Weeks 1, 4, 8 & 12 after fecal microbiota transplantation.;Change in gut microbiome alpha diversity, beta diversity, taxonomic composition & functional microbial profiles assessed using 16S ribosomal RNA sequencing & shotgun metagenomic sequencing.Timepoint: At baseline & at Weeks 1, 4, 8 & 12 after fecal microbiota transplantation.;Progression-free survival, defined as time from study enrolment to disease progression, recurrence or death from any cause.Timepoint: At Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 after enrolment.;Overall survival, defined as time from study enrolment to death from any cause.Timepoint: At Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 after enrolment. | — |
Countries
India
Contacts
Public ContactJosh Thomas Georgy
Christian Medical College, Vellore
Outcome results
None listed