The primary goal is to demonstrate that in gastric esophageal cancer the addition of a microbiome intervention with fecal capsules from healthy donors can improve the effectiveness of perioperative chemotherapy as measured by the tumor regression…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is pathological response to chemotherapy based on the tumor
regression grade. We look at the number of patients with a TRG 1-2 (complete or
subtotal response) in both arms.
Secondary outcome
Efficacy and mechanism of action of fecal capsules in combination with
chemotherapy for gastric and esophageal cancer.
-Pathological complete response (ypT0N0)
-R0 resection rate
-Progression-free survival and disease recurrence pattern
-Overall survival
-Incidence and severity of post-operative complications according to the
Clavien - Dindo classification.
-Percentage completion of preoperative chemotherapy treatment
-Percentage withdrawal rate from surgery
-Percentage delay of surgery
-Quality of life (EORTC QLQ-C30 summary score)
-Adverse events of preoperative chemotherapy treatment
Exploratory translational and exploratory biomarker research with tumor
biopsies, blood samples and fecal samples from patients. The primary purpose of
this is to understand the effect of these capsules on the tumor and the immune
system.
Tumor biopsies will be used to characterize the immune microenvironment by
immunohistochemical stains. Biopsies can be used for DNA and RNA sequencing to
investigate gene expression and mutations related to the effectiveness of the
capsules. Blood samples will be used to characterize PBMCs by flow cytometry,
quantify metabolites and measure cytokines. In addition, cell free DNA can be
isolated from blood plasma to detect circulating tumor DNA, which can be used
as a biomarker. The tumor biopsies and stool samples will also be used to
quantify bacterial populations using 16S sequencing. This will allow for the
microbiome to be mapped.
The stool from the fecal donors will also be examined to compare the microbiome
between patients and donors.
Background summary
Despite perioperative chemotherapy and resection, gastric esophageal cancer
remains a difficult condition to cure. There is increasing evidence that the
microbiome influences the tumor and response to therapy. In recent research we
have shown that a fecal microbiome transplant from a healthy donor prior to
palliative chemotherapy can improve response. In the CAPGO study we want to
investigate whether a patient-friendly microbiome intervention with fecal
capsules from allogeneic healthy donors can help chemotherapy work more
effectively. These capsules have previously been tested in patients with
diabetes, clostridium and colitis, where they were effective with few side
effects.
Study objective
The primary goal is to demonstrate that in gastric esophageal cancer the
addition of a microbiome intervention with fecal capsules from healthy donors
can improve the effectiveness of perioperative chemotherapy as measured by the
tumor regression grade.
Study design
This study is a randomized double-blind phase II study. Patients are divided
into two groups by drawing lots. Randomization will be done between adding
fecal capsules and placebo capsules. All patients receive standard
perioperative chemotherapy with 4 cycles before surgery and 4 cycles after
surgery. The capsules will be taken once a day for 7 days before each
preoperative chemotherapy treatment. This concerns a total period of 4 weeks
during which the capsules will be used.
Intervention
Fecal capsules from healthy donors. Patients should take one capsule once a day
for a total of 4 weeks prior to each preoperative chemotherapy treatment for 7
days. An operation will take place after 12 weeks. After the operation, regular
postoperative chemotherapy without capsules will be completed.
Study burden and risks
Taking blood samples and inserting an IV can be slightly painful and in some
cases cause a hematoma.
In rare cases, gastroscopy can result in bleeding or perforation.
Patients may experience side effects from the medication and the capsules.
Side effects associated with the standard of care FLOT chemotherapy are the
same as if people did not participate in the study. Include bone marrow
toxicity, gastrointestinal side effects, neuropathy, hair loss and allergic
reactions.
Side effects from the fecal capsules are mild and are mainly gastrointestinal
such as nausea, bloating or short-term diarrhea. In addition, there is a very
small chance that unknown pathogens are transferred from the allogeneic donors.
The donors are extensively screened to prevent this from happening and this has
not yet occurred in other studies with these capsules.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Patients
-Resectable adenocarcinoma of the stomach or gastro*esophageal junction;
planned start with neo-adjuvant FLOT
-Patient is fit for surgery
Healthy fecal donors
-Lean body mass of 80% or more
Exclusion criteria
Patients
Past (within 5 years) or current history of malignancy other than entry
diagnosis interfering with prognosis of gastro-esophageal cancer, not including
superficial and adequately treated skin and cervical malignancies.
History of a non-malignant disease of the digestive tract, such as celiac
disease, chronic diarrhoea (>=3 stools/day for >4 weeks), chronic obstipation
(<2 defecations/week for >3 months), Irritable Bowel Syndrome (IBS) (according
to Rome IV criteria) or Inflammatory Bowel Disease (IBD).
Uncontrolled (bacterial) infections
Healthy fecal donors
-Use of antibiotics
-Infections such as HIV, hepatitis B or C
-Smoking or drug use
-Parasite infection
-Gastro-intestinal diseases such as IBS or IBD
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL86412.018.24 |