Fecal Microbiota TransplantationNCT04577729
The IRMI-FMT Trial
A study testing Allogenic Fecal Microbiota Transplantation and Autologous Fecal Microbiota Transplantation in people with Fecal Microbiota Transplantation and Malignant Melanoma Stage III, run by Medical University of Graz at 1 site in Austria.
Trial summary
Aim of the study is to investigate the effect of Fecal Microbiota Transplantation (FMT) and Checkpoint Inhibitor (CI) re-challenge in prior CI refractory patients on Progression free survival (PFS) and tumor using donor stool of former malignant melanoma patients, who have been in remission due to CI treatment for at… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fecal Microbiota Transplantation, Malignant Melanoma Stage III, Malignant Melanoma Stage IV
- What is being tested?
- Allogenic Fecal Microbiota Transplantation and Autologous Fecal Microbiota Transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteAustria
- Study dates
- 21 May 2021to 7 Jun 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
- Patients with histologically confirmed malignant melanoma
- Age > 18 years
- Written consent of the participant after being informed
- Contraception as described in protocol appendix section VI
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): PS 0 to 1.
- Previously treated, unresectable stage III or stage IV melanoma as per the American Joint Committee on Cancer 2017 Guidelines (8th Edition) regardless of BRAF mutation status.
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- Patients must have experienced disease progression or recurrence during treatment with an anti-PD-1 monoclonal antibody, not having OR not willing to accept other approved systemic treatment options (like: BRAF and MEK inhibitors in BRAF V600 mutated melanoma).
- Patients with CNS (central nervous system) metastases:
- Patients are eligible if CNS metastases are treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks Prior to enrolment. In addition, patients must be either off corticosteroids or on a stable or decreasing dose <10 mg daily prednisone (or equivalent) OR
- Patients are eligible if they have previously untreated CNS metastases and are neurologically asymptomatic. In addition, patients must be either off corticosteroids or on a stable or decreasing dose of <10 mg daily prednisone (or equivalent) OR
- Patients with additional leptomeningeal metastases are eligible if they are treated and neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrolment and have an estimated life expectancy of at least 3 months. In addition, subjects must be either off corticosteroids or on a stable or decreasing dose of <10 mg daily prednisone (or equivalent)
- Patients must have evaluable disease by CT (computer tomography) or MRI (magnet resonance imaging) per RECIST 1.1 criteria (Appendix 3) (radiographic tumor assessment performed before as well as after 10 weeks of first dose of study drug) or clinically apparent disease that the investigator can follow for response.
Who cannot join
- Active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no MRI evidence of progression for at least 2 weeks after treatment is complete and within 28 days prior to first dose of study treatment administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study treatment administration. Stable dose of anticonvulsants is allowed. Treatment for CNS metastases may include stereotactic radiosurgery (e.g. GammaKnife, CyberKnife, or equivalent) or neurosurgical resection. Patients who received whole brain radiation therapy are not eligible.
- Prior treatment with chemotherapy, interferon (adjuvant setting), IL-2 (Interleukin-2), BRAF/MEK Inhibitors (v-Raf murine sarcoma viral oncogene homolog B/Mitogen-Activated Protein Kinase) for subjects with known BRAF V600 mutations, MEK inhibitors for NRAS (N-Rat sarcoma) mutations, and cKIT (Tyrosinkinase) Inhibitor subjects with known cKIT mutations is NOT allowed.
- Uveal melanoma is excluded.
- Coexisting severe chronic diseases other than melanoma (other neoplasias, autoimmune diseases,…).
- Secondary gastrointestinal motility disorders.
- Pregnancy and breast feeding.
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- Large abdominal surgery in medical history.
- Intake of any medication introduced by another clinical study.
- Any conditions (e.g. allergies), that do not allow the administration or intake of any of the substances used in this study (Nivolumab, Vancomycin, colonic lavage fluid).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: INDUCING REMISSION IN MELANOMA PATIENTS WITH CHECKPOINT INHIBITOR THERAPY USING FECAL MICROBIOTA TRANSPLANTATION.
Aim of the study is to investigate the effect of Fecal Microbiota Transplantation (FMT) and Checkpoint Inhibitor (CI) re-challenge in prior CI refractory patients on Progression free survival (PFS) and tumor using donor stool of former malignant melanoma patients, who have been in remission due to CI treatment for at least 1 year.
- Conditions
- Fecal Microbiota Transplantation, Malignant Melanoma Stage III, Malignant Melanoma Stage IV
- Being tested
- Allogenic Fecal Microbiota Transplantation, Autologous Fecal Microbiota Transplantation
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogenic Fecal Microbiota TransplantationProcedure or surgery
Patients receiving stool from prior malignant melanoma (MM) patients in remission for at least 1 year after Checkpoint Inhibitor Treatment.
Autologous Fecal Microbiota TransplantationProcedure or surgery
Patients receiving their own stool in terms of sham FMT.
| Study group | Role | What they receive |
|---|---|---|
| Allogenic FMT group | Experimental | Allogenic FMT group: patients receiving stool from prior malignant melanoma (MM) patients in remission for at least 1 year after Checkpoint Inhibitor Treatment. Receives: Procedure: Allogenic Fecal Microbiota Transplantation |
| Autologous FMT group | Placebo comparator | Autologous FMT group: patients receiving their own stool in terms of sham FMT. Receives: Procedure: Autologous Fecal Microbiota Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
Patients undergoing CI therapy after FMT will be evaluated by Immune-RECIST (iRECIST) criteria after contrast-enhanced CT-scan in order to determine disease progression.
Measured: 3 months after checkpoint inhibitor (CI) therapy following fecal microbiota transplantation (FMT).
Secondary outcomes (6)
Tumor response (CR, PR, SD)
Complete response (CR), partial response (PR) and stable disease (SD) of target or non-target lesions are considered tumor response in this trial according to iRECIST criteria after three months.
Measured: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Detection of specific donor signaling in intestinal microbiota leading to response to CI therapy.
A total of five donors will be included in the study. The allogenic-FMT group will receive donor stool from a single donor per patient for both, the primary FMT and a scheduled booster FMT. Donors will be divided into those, who successfully improved PFS and/or tumor response versus those, who were not able to induce treatment response. Donor stool will be evaluated by 16s-RNA analysis.
Measured: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Detection of specific patients' microbiota pre and post FMT leading to response.
Patients will be divided into responders and nonresponders and microbiota will be analyzed via 16s-RNA analysis before and after FMT. We will look into specific donor-signaling in patients stool samples after FMT, as well as trying to identify groups of intestinal microbiota associated with higher response rates to CI re-challenge.
Measured: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Frequency of Adverse Events categorized according to the CTCAE grading system Version 4.0
To evaluate safety and toxicity of CI therapy after FMT vs. control group. Drug toxicity will be monitored, categorized according to the CTCAE grading system Version 4.0 and managed according to recent recommendations by the SITC Toxicity Management Working Group.
Measured: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Serum Neutrophil-to-Lymphocyte Ratio (NLR) pre- and post-FMT as an indicator for response.
In our study we will look at potential alterations in NLR after FMT and whether this can indicate response to CI treatment after FMT.
Measured: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Detection of differences between primary and secondary non-responders to CI therapy and their specific outcome after FMT by performing a subgroup analysis.
To date and according to present data we do not know, whether primary or secondary non-responders may have a better potential to respond to FMT in order to reach PFS under CI rechallenge. Hence, a subgroup analysis will be performed, in order to identify patient groups best suited for such treatment in the future.
Measured: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start21 May 2021
- Primary completion7 Jun 2023
- Study completion7 Jun 2023
Why it stopped: Agreement with project partner prematurely cancelled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fecal Microbiota TransplantationStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Graz
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04577729
- Sponsor's protocol ID
- CA-209-7HP
- Status last verified
- Jul 2023
- First submitted
- 30 Sep 2020
- Last updated
- 10 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INDUCING REMISSION IN MELANOMA PATIENTS WITH CHECKPOINT INHIBITOR THERAPY USING FECAL MICROBIOTA TRANSPLANTATION.
- ClinicalTrials.gov ID
- NCT04577729
- Acronym / sponsor ID
- CA-209-7HP
- Conditions
- Fecal Microbiota Transplantation, Malignant Melanoma Stage III, Malignant Melanoma Stage IV
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Agreement with project partner prematurely cancelled.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Medical University of GrazUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 21 May 2021 (actual)
- Primary completion
- 7 Jun 2023 (actual)
- Study completion
- 7 Jun 2023 (actual)
- First posted
- 8 Oct 2020 (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.
Aim of the study is to investigate the effect of Fecal Microbiota Transplantation (FMT) and Checkpoint Inhibitor (CI) re-challenge in prior CI refractory patients on Progression free survival (PFS) and tumor using donor stool of former malignant melanoma patients, who have been in remission due to CI treatment for at least 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Allogenic FMT group | Experimental | Procedure: Allogenic Fecal Microbiota TransplantationAllogenic FMT group: patients receiving stool from prior malignant melanoma (MM) patients in remission for at least 1 year after Checkpoint Inhibitor Treatment. |
| Autologous FMT group | Placebo comparator | Procedure: Autologous Fecal Microbiota TransplantationAutologous FMT group: patients receiving their own stool in terms of sham FMT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with histologically confirmed malignant melanoma
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): PS 0 to 1.
- Previously treated, unresectable stage III or stage IV melanoma as per the American Joint Committee on Cancer 2017 Guidelines (8th Edition) regardless of BRAF mutation status.
- Patients must have experienced disease progression or recurrence during treatment with an anti-PD-1 monoclonal antibody, not having OR not willing to accept other approved systemic treatment options (like: BRAF and MEK inhibitors in BRAF V600 mutated melanoma).
- Patients with CNS (central nervous system) metastases:
Key exclusion criteria (9 listed)
- Active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no MRI evidence of progression for at least 2 weeks after treatment is complete and within 28 days prior to first dose of study treatment administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study treatment administration. Stable dose of anticonvulsants is allowed. Treatment for CNS metastases may include stereotactic radiosurgery (e.g. GammaKnife, CyberKnife, or equivalent) or neurosurgical resection. Patients who received whole brain radiation therapy are not eligible.
- Prior treatment with chemotherapy, interferon (adjuvant setting), IL-2 (Interleukin-2), BRAF/MEK Inhibitors (v-Raf murine sarcoma viral oncogene homolog B/Mitogen-Activated Protein Kinase) for subjects with known BRAF V600 mutations, MEK inhibitors for NRAS (N-Rat sarcoma) mutations, and cKIT (Tyrosinkinase) Inhibitor subjects with known cKIT mutations is NOT allowed.
- Uveal melanoma is excluded.
- Coexisting severe chronic diseases other than melanoma (other neoplasias, autoimmune diseases,…).
- Secondary gastrointestinal motility disorders.
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 |
|---|---|---|
| Allogenic Fecal Microbiota TransplantationPatients receiving stool from prior malignant melanoma (MM) patients in remission for at least 1 year after Checkpoint Inhibitor Treatment. | Procedure or surgery | Allogenic FMT group |
| Autologous Fecal Microbiota TransplantationPatients receiving their own stool in terms of sham FMT. | Procedure or surgery | Autologous FMT group |
Primary outcome
Progression free survival (PFS)
Time frame: 3 months after checkpoint inhibitor (CI) therapy following fecal microbiota transplantation (FMT).
Patients undergoing CI therapy after FMT will be evaluated by Immune-RECIST (iRECIST) criteria after contrast-enhanced CT-scan in order to determine disease progression.
6 secondary outcomes
Tumor response (CR, PR, SD)
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Detection of specific donor signaling in intestinal microbiota leading to response to CI therapy.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Detection of specific patients' microbiota pre and post FMT leading to response.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Frequency of Adverse Events categorized according to the CTCAE grading system Version 4.0
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Serum Neutrophil-to-Lymphocyte Ratio (NLR) pre- and post-FMT as an indicator for response.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Detection of differences between primary and secondary non-responders to CI therapy and their specific outcome after FMT by performing a subgroup analysis.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Results and safety
The study was stopped early (reason given: Agreement with project partner prematurely cancelled.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2023.
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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 Allogenic Fecal Microbiota Transplantation and Autologous Fecal Microbiota Transplantation in people with Fecal Microbiota Transplantation and Malignant Melanoma Stage III, run by Medical University of Graz at 1 site in Austria.
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 12 inclusion and 9 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: stopped early, as of the sponsor's last update on 10 Jul 2023. 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 Austria. 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: Agreement with project partner prematurely cancelled.). Results are not available in the source record.
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?
Progression free survival (PFS) (time frame: 3 months after checkpoint inhibitor (CI) therapy following fecal microbiota transplantation (FMT).). 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 10 Jul 2023.