Gastroesophageal cancer, Cancer cachexia Stomach and esophageal cancer, Unintended weight and muscle loss due to cancer
Conditions
Interventions
The investigational product is the addition of capsules containing lyophilized allogenic faecal matter. These capsules will be taken once daily, starting on the first day of the first chemotherapy cyc
Screened healthy donors will deliver feces to the investigators at the Amsterdam UMC, lo-cation Meibergdreef. Feces from approximately 20 donors will be pooled before pro-cessing. The allogenic feces
Sponsors
Amsterdam UMC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients:Histologically confirmed inoperable/irresectable and/or metastatic adenocarcinoma of the stomach or esophagusPlanned to receive second-line palliative chemotherapy with paclitaxel and ramucirumabECOG/WHO performance status 0, 1, or 2Age = 18 yearsAdequate hematological, renal, and hepatic function defined as:Neutrophils = 1.5 x 10^9/LPlatelets = 100 x 10^9/LHemoglobin = 5.0 mmol/LTotal bilirubin = 1.5 x upper normal limit Creatinine clearance (Cockcroft-Gault) > 50 ml/minWritten, voluntary informed consent Expected adequacy of follow-up and ability to comply with study procedures Stable medication use Donors Age: =18 years oldBMI <25 kg/m2Potential donors should be able to give informed consent
Exclusion criteria
Exclusion criteria: Patients Past (within 5 years) or current history of malignancy other than the entry diagnosis interfering with prognosis of gastroesophageal cancerPrevious chemotherapy for other cancers within the last six monthsSignificant concomitant diseases preventing safe administration of LFMC or likely to interfere with study assessmentsUncontrolled angina pectoris, cardiac failure, or clinically significant arrhythmiasContinuous use of immunosuppressive agents equivalent to >10 mg daily prednisone if used for reasons unrelated to the malignancy or its chemotherapy regimenConcurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudineNeurotoxicity > CTC grade 1Dementia or altered mental status prohibiting understanding and giving informed consentInadequate caloric and/or fluid intake despite consultation with a dietician and/or tube feedingCompromised immunity due to human immunodeficiency virus (HIV) infection with CD4 count < 240/mm³History of non-malignant digestive tract disease such as celiac disease, chronic diarrhea (=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, sepsis. Use of pro-/prebiotics in the past three months or during the study periodUse of >21 units of alcohol per week on average in the past three monthsPregnancy or breastfeedingDonorsUse of any medication including proton pump inhibitors, antibiotics and pro-/prebiotics in the past three months or during the study periodHistory of, or known exposure to HIV, hepatitis B (HBV) or C virus (HCV), syphilis, human T-lymphotropic virus (HTLV) I and II, malaria, trypanosomiasis, tuberculosisKnown systemic infection not controlled at the time of donationSmoking or illicit drug use (MDMA/amphetamine/cocaine/heroin/GHB) in the past three months or use during the study periodUse of >5 units of alcohol daily on average in the past three months or use of >2 units of alcohol during the study periodRisky sexual behavior (including anonymous sexual contacts; sexual contacts with sex workers, individuals who use intravenous drugs, or persons with HIV, viral hepatitis, or syphilis; occupation as a sex worker; or a history of sexually transmitted infections)Previous reception of tissue/organ transplantPrevious (<12 months) reception of blood productsRecent (<6 months) needle stick accidentRecent (<6 months) body tattoo, piercing, earring, acupunctureRecent medical treatment in poorly hygienic conditionsRisk of transmission of diseases caused by prionsRecent parasitosis or infection from rotavirus, Giardia lamblia and other microbes with GI involvementRecent travel in tropical countries, countries at high risk of communicable diseases or traveler’s diarrhea (period based on recommendations Sanquin for blood donors)Recent (<6 months) history of vaccination with a live attenuated virus, if there is a possible risk of transmissionHealthcare providers having frequent patient contact (to exclude the risk of transmission of multidrug-resistant organisms)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary outcomeThe primary endpoint is the differential change in body mass index between baseline and 12 weeks in GEC patients either treated with oral encapsulated FMT vs those treated with placebo capsules, in addition to second-line palliative chemotherapy with paclitaxel and ramucirumab. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcomesDifferential change in fat-free mass (index) from baseline to 12 weeks, assessed via bioimpedance analysis (BIA)Changes in radiologically-assessed body composition (derived from on clinically grounds performed CT body scans) at baseline as well as 12 and 24 weeks, involving changes skeletal muscle cross-sectional area (CSA) and adjusted skeletal muscle index (ASMI)Skeletal muscle mitochondrial oxidative capacity (OXPHOS) and gene expression assessed via single-nucleus sequencing (snRNA-seq), evaluated in fine needle muscle biopsies obtained at baseline and week 12Skeletal muscle fiber type composition and atrophy assessed via myosin ATPase and laminin staining, respectively, in biopsies obtained at baseline and week 12Effect of FMT capsules in addition to second-line chemotherapy on specific changes in parameters of appetite (SNAQ) and satiety (Hunger and Satiety Visual Analogue Scales (VAS)) at baseline and weeks 4, 12 and 24Effect of FMT capsules on the development of clinical cancer-related cachexia in study participants without cachexia at baseline. Presence of cachexia will be defined based on simplified clinical criteria adapted from Fearon et al. (Lancet Oncol. 2011;12(5):489-495) [7], modified for clinical availability and practicalityWeight loss >5% over past 6 months in the absence of simple starvation OR BMI <20 kg/m2 and any degree of weight loss >2%Effect of these capsules on oncological endpoints, including progression free survival (PFS), overall survival (OS), disease control rate (DCR), ECOG performance status, quality of life (EORTC QLQ-C30) and hospitalizations up to 2 years following interventionSerum cytokine profiling (IL-6, TNF-a, IL-1ß, IL-10, GDF15) at baseline, weeks 4, 12, and 24 PBMC assays (gene expression and ex vivo stimulated cytokine production) at baseline, weeks 4, 12, and 24Muscle strength (handgrip strength assessed via dynamometer) at baseline and weeks 4, 12 and 24Vagal nerve tone, assessed via c | — |
Countries
Netherlands
Contacts
Public ContactM. Nieuwdorp
Amsterdam UMC
Outcome results
None listed