NCT04924374

Microbiota Transplant in Advanced Lung Cancer Treated With Immunotherapy

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations in patients with advanced lung cancer through fecal microbiota transplantation from healthy individuals or from long-term survivors to advanced lung cancer will enhance the efficacy of immunotherapy.

Detailed description

Lung cancer is a leading cause of mortality worldwide, and its treatment and prognosis are being revolutionized by immunotherapy. The gut microbiome has been shown able to modulate the antitumor efficacy of immunotherapeutic agents in pre-clinical models, demonstrating that patients can be stratified into responders and nonresponders to immunotherapy on the basis of their microbiota composition. Fecal microbiota transplants have demonstrated to improve the efficacy of immunotherapy in animal models. In this study, investigators will include 20 stage III/V non-small cell lung cancer naïve for PD/PD L-1 inhibitors that require treatment in monotherapy or combined with chemotherapy as consolidation strategy after concurrent chemotherapy and radiotherapy (stage III), upfront treatment (stage IV patients with PDL1 status \> 50%) or as second line strategy for those patients with advanced disease who progressed to chemotherapy alone. The participants will be randomized to receive either fecal microbiota capsules from 3 donors selected based on the fecal abundance of bacterial taxa shown to correlate with a greater response to immunotherapy or not, in combination with the PDL/PDL1 agent. The primary outcome will be safety. The secondary outcomes will be treatment response (iRECIST criteria). Investigators will also examine engraftment of donor's microbiota on host microbiota using Illumina DNA shotgun sequencing, changes in the bacterial metabolism using metaproteomics, and in the plasma metabolite fingerprint by untargeted mass spectrometry in bacterial and plasma samples, and changes in peripheral immune cells subpopulations and antitumoral immunity. MORELIA could improve the prognosis of a lung cancer in a subset of patients with limited therapeutic options and inform on how to exploit host-microbiota interactions with tailored fecal microbiota transplantation to boost the clinical response to immunotherapy in advanced cancer.

Conditions

• Lung Cancer

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Microbiota Transplant plus anti PD1 therapy	Pooled fecal microbiota capsules of 1 donor selected based on their fecal abundance in Faecalibacterium prausnitzii, Bifidobacterium longum, Akkermansia muciniphila and Fusobacterium spp. after screening and metagenomic analysis of 10 donors with high-fiber diets (\>30g/day). anti PD1 therapy every 2-3 weeks
DRUG	anti PD1 therapy	anti PD1 therapy every 2-3 weeks

Timeline

• Start date: 2021-04-23
• Primary completion: 2023-11-15
• Completion: 2023-11-15
• First posted: 2021-06-14
• Last updated: 2024-09-26

Locations

1 site across 1 country: Spain