Lung CancerNCT04924374
Microbiota Transplant in Advanced Lung Cancer Treated With Immunotherapy
A study testing Microbiota Transplant plus anti PD1 therapy and anti PD1 therapy in people with Lung Cancer, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Microbiota Transplant plus anti PD1 therapy and anti PD1 therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteSpain
- Study dates
- 23 Apr 2021to 15 Nov 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Adequate bone marrow, renal, liver and metabolic parameters (evaluated at least 7 days prior the inclusion in the study:
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Microbiota Transplant plus anti PD1 therapy, anti PD1 therapy
- Keywords
- Oncology, Fecal Microbiota Transplantation, Metabolomics, Chemotherapy, Lung Cancer, Immunotherapy, Immunosenescence, Microbiota, Metagenomics, Metaproteomics
- Medical subject headings
- Lung Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Microbiota Transplant plus anti PD1 therapyDietary supplement
Also called anti PD1 therapy Pembrolizumab, Nivolizumab, Atezolizumab
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
anti PD1 therapyDrug
Also called Pembrolizumab, Nivolizumab, Atezolizumab
anti PD1 therapy every 2-3 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Dietary Supplement: Microbiota Transplant plus anti PD1 therapy |
| anti PD1 therapy | Active comparator | Control arm: no intervention before anti PD1 therapy Receives: Drug: anti PD1 therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 27 weeks
Secondary outcomes (1)
Measure of Efficacy
Immunotherapy Response Evaluation Criteria in Solid Tumors-iRECIST
Measured: 27 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2021
- Study start23 Apr 2021
- Primary completion15 Nov 2023
- Study completion15 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04924374
- Sponsor's protocol ID
- MORELIA
- Status last verified
- Sep 2024
- First submitted
- 7 May 2021
- Last updated
- 26 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microbiota Transplant in Advanced Lung Cancer Treated With Immunotherapy
- ClinicalTrials.gov ID
- NCT04924374
- Acronym / sponsor ID
- MORELIA
- Conditions
- Lung Cancer
- Keywords
- Oncology, Fecal Microbiota Transplantation, Metabolomics, Chemotherapy, Lung Cancer, Immunotherapy, Immunosenescence, Microbiota
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Study start
- 23 Apr 2021 (actual)
- Primary completion
- 15 Nov 2023 (actual)
- Study completion
- 15 Nov 2023 (actual)
- First posted
- 14 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| anti PD1 therapy plus Microbiota Transplant | Experimental | Dietary Supplement: Microbiota Transplant plus anti PD1 therapyActive 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 |
| anti PD1 therapy | Active comparator | Drug: anti PD1 therapyControl arm: no intervention before anti PD1 therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Microbiota Transplant plus anti PD1 therapyAlso: anti PD1 therapy Pembrolizumab, Nivolizumab, AtezolizumabPooled 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 | anti PD1 therapy plus Microbiota Transplant |
| anti PD1 therapyAlso: Pembrolizumab, Nivolizumab, Atezolizumabanti PD1 therapy every 2-3 weeks | Drug | anti PD1 therapy |
Primary outcome
Measure of safety
Time frame: 27 weeks
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
1 secondary outcome
Measure of Efficacy
Time frame: 27 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Microbiota Transplant plus anti PD1 therapy and anti PD1 therapy in people with Lung Cancer, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure of safety (time frame: 27 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2024.