Microbiota Transplant in Advanced Lung Cancer Treated With Immunotherapy

NCT04924374 | Completed

• 1 other identifier: MORELIA
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lung Cancer

Keywords

Oncology; Fecal Microbiota Transplantation; Metabolomics; Chemotherapy; Lung Cancer; Immunotherapy; Immunosenescence; Microbiota; Metagenomics; Metaproteomics

Outcome Measures

Primary Outcomes (1)

• Measure of safety

  The safety variables (vital signs, physical examinations, symptoms, laboratory test results and the occurrence of adverse events) will be assessed at each visit. The incidence of adverse events will be categorized by severity and related to the time of occurrence. Changes in physical examinations, changes in laboratory test results (hematology, biochemistry and urinalysis tests) from screening period, and change of vital signs will be summarized and analyzed by the descriptive statistics. Adverse events will be defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. v5.0

  27 weeks

Secondary Outcomes (1)

• Measure of Efficacy

  27 weeks

Study Arms (2)

anti PD1 therapy plus Microbiota Transplant

EXPERIMENTAL

Active arm: 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

Dietary Supplement: Microbiota Transplant plus anti PD1 therapy

anti PD1 therapy

ACTIVE COMPARATOR

Control arm: no intervention before anti PD1 therapy

Drug: anti PD1 therapy

Interventions

Microbiota Transplant plus anti PD1 therapy DIETARY_SUPPLEMENT

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

Also known as: anti PD1 therapy Pembrolizumab, Nivolizumab, Atezolizumab

anti PD1 therapy plus Microbiota Transplant

anti PD1 therapy DRUG

anti PD1 therapy every 2-3 weeks

Also known as: Pembrolizumab, Nivolizumab, Atezolizumab

anti PD1 therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to sign the informed consent
• Age \>18 years.
• Diagnosis of unresectable stage III non-small cell cancer histologically or citologically confirmed.
• Eastern Cooperative Oncology Group (ECOG) Score ≤1
• Disease able to be monitored using the RECIST v.1.1. criteria (lesions treated with radiotherapy can be defined as target lesions if the progression has been documented).
• At least 3 weeks since the last treatment for cancer, including chemotherapy and radiotherapy when combined in stage III patients, and recovery ≤1 from any adverse event related with previous treatment for cancer, excluding sensorial neuropathy, anemia, asthenia, hair loss, all grade ≤2), according to the National Cancer Institute (CTCAE del NCI, v.5) definitions
• Platelet count ≥100 x 109/l, hemoglobin ≥9 g/dl and absolute neutrophil count ≥1,000 x 109/l.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times the upper limit of normality, independently of the presence of liver metastases.
• Alkaline phosphatase ≤ 2,5 times the upper limit of normality.
• Total bilirubin ≤1,5 times the upper limit of normality o direct bilirubin below the upper level of normality.
• INR\<1,5, except if concomitant oral anticoagulation
• Estimated glomerular filtration rate ≥30 ml/minute using the EPI equation
• Albumin ≥3 g/dl without previous parenteral albumin treatment.
• All men and women with childbearing potential must accept the use of highly efficacious contraceptive methods during the study.

You may not qualify if:

• Active of untreated central nervous system (CNS) involvement. Treated CNS metastases must be radiologically stable (defined as the absence of CNS progression during at least 3 weeks from the first CNS imaging after radiotherapy to the CNS imaging prior the screening visit. Participants will not be included in the presence of any neurological sign or symptom secondary to CNS metastases or radiotherapy. Any treatment with steroids must have been completed at least 14 days before the first study intervention.
• Prior use of immunotherapy of immunomodulatory treatment for non-small cell lung cancer, either in combination or in monotherapy, at any stage of the disease.
• Radiotherapy in \>35% the bone marrow.
• Prior bone marrow or cell-stem transplant.
• Treatment with immunoestimulatory agents, including interferons or interleukin-2 before 4 weeks or 5 drug half-lives (whichever longer) before the randomization.
• Prior neoplasia, with the exception of skin basocelular carcinoma, superficial bladder carcinoma, squamous cell skin carcinoma, cervix high degree intrasquamous lesion. Those patients with prior neoplasia free of recurrence during at least 2 years are eligible.
• Severe infections four weeks before the screening, including hospitalization due to any infection, bacteremia or severe pneumonia.
• Rectal colonization by vancomycin resistant enterococci
• Overt immunodeficiency, including systemic treatment with steroids at \>10 mg of prednisone/day (or its equivalent) or other immunosuppressive agents during the 14 days before the first study intervention.
• Moderates-severe mucositis , GI symptoms
• Dysphagia, history of aspirative pneumonia

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead

Study Sites (1)

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

MeSH Terms

Conditions

Lung Neoplasms; Neoplasms

Interventions

atezolizumab; pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: June 14, 2021
• Study Start: April 23, 2021
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: September 26, 2024

Record last verified: 2024-09

Locations

ES (1)