Diarrhea Caused by Drug (Disorder)NCT04040712
Fecal Microbiota Transplantation in Diarrhea Induced by Tyrosine-kinase Inhibitors
A study testing Donor FMT in people with Diarrhea Caused by Drug (Disorder) and Renal Cell Cancer, run by Catholic University of the Sacred Heart at 1 site in Italy.
Trial summary
Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with metastatic renal cell carcinoma, and are commonly used as first-line option for this condition, but their use is encumbered by side effects, mainly diarrhea, for which there are no standardized strategies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diarrhea Caused by Drug (Disorder), Renal Cell Cancer
- What is being tested?
- Donor FMT
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 2 Aug 2019to 5 Feb 2020
- 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
- 18 years old or older
- treatment with pazopanib or sunitinib for metastatic RCC diagnosed at histology and measurable according to RECIST criteria version 1.1
- development of diarrhea of 2-3 grade according to Common Terminology Criteria (CTC) for Adverse Events (AE) version 4.0 induced by these drugs.
- execution of a CT scan no earlier than 4 weeks before enrollment
- good or intermediate prognostic assessment (according to criteria of the prognostic system of the International Metastatic RCC Database Consortium)
- performance status equal or lower than 2
- blood count, hepatic and kidney testing within normal limit
- ability to give their consent to be included in the study.
Who cannot join
- another known cause of diarrhea (e.g. infectious gastroenteritis. Clostridium difficile infection, celiac disease, inflammatory bowel disease, irritable bowel syndrome, chronic pancreatitis, biliary salt diarrhea)
- previous colorectal surgery or cutaneous stoma
- food allergies
- recent (<6 weeks) therapy with drugs that could possibly alter gut microbiota (e.g. antibiotics, probiotics, proton pump inhibitors, immunosuppressants, metformin)
- another cancer (except for surgically treated basocellular carcinoma)
- brain metastases
Show all 11Show fewer
- decompensated heart failure or heart disease with ejection fraction lower than 30%
- severe respiratory insufficiency
- psychiatric disorders
- pregnancy
- unable to give informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Fecal Microbiota Transplantation to Treat Diarrhea Induced by Tyrosine-kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma: a Randomized Clinical Trial.
Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with metastatic renal cell carcinoma, and are commonly used as first-line option for this condition, but their use is encumbered by side effects, mainly diarrhea, for which there are no standardized strategies. Increasing evidence suggests that gut microbiota could influence the development of TKIs-induced diarrhea. In theory, the therapeutic modulation of gut microbiota could be an approach to alleviate TKI-induced diarrhea. Fecal microbiota transplantation (FMT) is the infusion of fecal microbiota from a healthy donor in the gut of a recipient with the aim of curing a specific disease. It has been increasingly recognized as a highly effective treatment against recurrent Clostridium difficile infection.To date, the effects of FMT on chemotherapy-related diarrhea are unknown. This study will evaluate, through a randomized controlled design, the efficacy of fecal microbiota transplantation (FMT), compared with sham FMT, in treating TKI-induced diarrhea in patients with metastatic renal cell carcinoma.
Read the detailed description
Despite the improvement in diagnosis and management, renal cell carcinoma (RCC) remains one of the most burdensome urological cancers, being the sixth most common malignancy in men and the 10th in women, accounting, respectively, for 5% and 3% of all cancers. Moreover, the incidence of RCC is increasing, especially in Western countries, accounting for nearly 60000 new cases per year in the United States. A considerable proportion of patients present with metastatic disease at diagnosis, and there are more than 140000 RCC-dependent deaths per year worldwide according to the World Health Organization.
Sunitinib and pazopanib are oral multi-targeted receptor tyrosine kinase inhibitors (TKIs) that have dramatically improved the survival of patients with metastatic RCC, and are commonly used as first-line option for this condition.
However, long-term use of these drugs is prevented by the development of toxicity. Diarrhea is one of the most common side effects of TKIs, occurring in nearly 50% of patients. It decreases the quality of life of these patients, and often requires dose reduction and drug discontinuation, potentially decreasing the efficacy of TKIs.
To date there are no standardized strategies for TKIs-related diarrhea, and current recommendations are supported by few evidence or real-life experience. Recommended treatment options include anti-motility agents, which are not targeted to act on the pathogenic pathways of diarrhea.
Increasing evidence suggests that gut microbiota could influence the development of TKIs-induced diarrhea. Overall, chemotherapy is known to drive, through the development of mucositis, deep compositional and functional alterations of gut microbiota. Mucositis occurs commonly after treatment with TKIs, and a specific dysbiotic profile has been found in patients with TKIs-induced diarrhea.
In theory, the therapeutic modulation of gut microbiota could be an approach to alleviate TKI-induced diarrhea. Although probiotics have been suggested as a possible treatment option for this condition, few evidence supports this indication.
Fecal microbiota transplantation (FMT) is the infusion of fecal microbiota from a healthy donor in the gut of a recipient with the aim of curing a specific disease. It has been increasingly recognized as a highly effective treatment against recurrent Clostridium difficile infection.
FMT has been also examined as a potential approach for other disorders associated with a disruption of gut microbiota, including ulcerative colitis or metabolic syndrome.
To date, the effects of FMT on chemotherapy-related diarrhea are unknown. The aim of this study is to investigate the efficacy of fecal microbiota transplantation (FMT), compared with sham FMT, in treating TKI-induced diarrhea in patients with metastatic RCC
- Being tested
- Donor FMT, Sham FMT
- Keywords
- fecal microbiota transplantation, microbiota, chemotherapy, diarrhea, renal cell carcinoma
- Medical subject headings
- Carcinoma, Renal Cell, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor FMTOther
Fecal microbiota transplantation using stools from healthy donors
Sham FMTOther
Sham fecal microbiota transplantation
| Study group | Role | What they receive |
|---|---|---|
| Donor FMT | Experimental | Fecal microbiota transplantation using stools from healthy donors Receives: Other: Donor FMT |
| Sham FMT | Sham comparator | Sham fecal microbiota transplantation Receives: Other: Sham FMT |
What is being measured
The primary outcome is the main question the study is designed to answer.
rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments
rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments
Measured: 4 weeks
Secondary outcomes (8)
rate of patients who need to stop or reduce treatment with tyrosine-kinase inhibitors
rate of patients who need to stop or reduce treatment with tyrosine-kinase inhibitors
Measured: 4 weeks
rate of patients who experience resolution of diarrhea 1 week after the end of treatments
rate of patients who experience resolution of diarrhea 1 week after the end of treatments
Measured: 1 week
rate of patients who experience resolution of diarrhea 2 weeks after the end of treatments
rate of patients who experience resolution of diarrhea 2 weeks after the end of treatments
Measured: 2 weeks
rate of patients who experience resolution of diarrhea 8 weeks after the end of treatments
rate of patients who experience resolution of diarrhea 8 weeks after the end of treatments
Measured: 8 weeks
rate of patients who experience decrease of diarrhea until grade G1 or lower 1 week after the end of treatments
rate of patients who experience decrease of diarrhea until grade G1 or lower 1 week after the end of treatments
Measured: 1 week
rate of patients who experience decrease of diarrhea until grade G1 or lower 2 weeks after the end of treatments
rate of patients who experience decrease of diarrhea until grade G1 or lower 2 weeks after the end of treatments
Measured: 2 weeks
rate of patients who experience decrease of diarrhea until grade G1 or lower 4 weeks after the end of treatments
rate of patients who experience decrease of diarrhea until grade G1 or lower 4 weeks after the end of treatments
Measured: 4 weeks
rate of patients who experience decrease of diarrhea until grade G1 or lower 8 weeks after the end of treatments
rate of patients who experience decrease of diarrhea until grade G1 or lower 8 weeks after the end of treatments
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2019
- Study start2 Aug 2019
- Primary completion5 Jan 2020
- Study completion5 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diarrhea Caused by Drug (Disorder)Studies 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
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catholic University of the Sacred Heart
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Cammarota, Catholic University of the Sacred Heart
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04040712
- Sponsor's protocol ID
- FMT-TKI-001
- Status last verified
- Mar 2020
- First submitted
- 22 Apr 2019
- Last updated
- 17 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ianiro G, Rossi E, Thomas AM, Schinzari G, Masucci L, Quaranta G, Settanni CR, Lopetuso LR, Armanini F, Blanco-Miguez A, Asnicar F, Consolandi C, Iacovelli R, Sanguinetti M, Tortora G, Gasbarrini A, Segata N, Cammarota G. Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma. Nat Commun. 2020 Aug 28;11(1):4333. doi: 10.1038/s41467-020-18127-y.
PubMed 32859933
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fecal Microbiota Transplantation to Treat Diarrhea Induced by Tyrosine-kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma: a Randomized Clinical Trial.
- ClinicalTrials.gov ID
- NCT04040712
- Acronym / sponsor ID
- FMT-TKI-001
- Keywords
- fecal microbiota transplantation, microbiota, chemotherapy, diarrhea, renal cell carcinoma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Catholic University of the Sacred HeartUniversity, hospital or other
- Study start
- 2 Aug 2019 (actual)
- Primary completion
- 5 Jan 2020 (actual)
- Study completion
- 5 Feb 2020 (actual)
- First posted
- 1 Aug 2019 (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.
Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with metastatic renal cell carcinoma, and are commonly used as first-line option for this condition, but their use is encumbered by side effects, mainly diarrhea, for which there are no standardized strategies. Increasing evidence suggests that gut microbiota could influence the development of TKIs-induced diarrhea. In theory, the therapeutic modulation of gut microbiota could be an approach to alleviate TKI-induced diarrhea. Fecal microbiota transplantation (FMT) is the infusion of fecal microbiota from a healthy donor in the gut of a recipient with the aim of curing a specific disease. It has been increasingly recognized as a highly effective treatment against recurrent Clostridium difficile infection.To date, the effects of FMT on chemotherapy-related diarrhea are unknown. This study will evaluate, through a randomized controlled design, the efficacy of fecal microbiota transplantation (FMT), compared with sham FMT, in treating TKI-induced diarrhea in patients with metastatic renal cell carcinoma.
Detailed description
Despite the improvement in diagnosis and management, renal cell carcinoma (RCC) remains one of the most burdensome urological cancers, being the sixth most common malignancy in men and the 10th in women, accounting, respectively, for 5% and 3% of all cancers. Moreover, the incidence of RCC is increasing, especially in Western countries, accounting for nearly 60000 new cases per year in the United States. A considerable proportion of patients present with metastatic disease at diagnosis, and there are more than 140000 RCC-dependent deaths per year worldwide according to the World Health Organization.
Sunitinib and pazopanib are oral multi-targeted receptor tyrosine kinase inhibitors (TKIs) that have dramatically improved the survival of patients with metastatic RCC, and are commonly used as first-line option for this condition.
However, long-term use of these drugs is prevented by the development of toxicity. Diarrhea is one of the most common side effects of TKIs, occurring in nearly 50% of patients. It decreases the quality of life of these patients, and often requires dose reduction and drug discontinuation, potentially decreasing the efficacy of TKIs.
To date there are no standardized strategies for TKIs-related diarrhea, and current recommendations are supported by few evidence or real-life experience. Recommended treatment options include anti-motility agents, which are not targeted to act on the pathogenic pathways of diarrhea.
Increasing evidence suggests that gut microbiota could influence the development of TKIs-induced diarrhea. Overall, chemotherapy is known to drive, through the development of mucositis, deep compositional and functional alterations of gut microbiota. Mucositis occurs commonly after treatment with TKIs, and a specific dysbiotic profile has been found in patients with TKIs-induced diarrhea.
In theory, the therapeutic modulation of gut microbiota could be an approach to alleviate TKI-induced diarrhea. Although probiotics have been suggested as a possible treatment option for this condition, few evidence supports this indication.
Fecal microbiota transplantation (FMT) is the infusion of fecal microbiota from a healthy donor in the gut of a recipient with the aim of curing a specific disease. It has been increasingly recognized as a highly effective treatment against recurrent Clostridium difficile infection.
FMT has been also examined as a potential approach for other disorders associated with a disruption of gut microbiota, including ulcerative colitis or metabolic syndrome.
To date, the effects of FMT on chemotherapy-related diarrhea are unknown. The aim of this study is to investigate the efficacy of fecal microbiota transplantation (FMT), compared with sham FMT, in treating TKI-induced diarrhea in patients with metastatic RCC
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donor FMT | Experimental | Other: Donor FMTFecal microbiota transplantation using stools from healthy donors |
| Sham FMT | Sham comparator | Other: Sham FMTSham fecal microbiota transplantation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18 years old or older
- treatment with pazopanib or sunitinib for metastatic RCC diagnosed at histology and measurable according to RECIST criteria version 1.1
- development of diarrhea of 2-3 grade according to Common Terminology Criteria (CTC) for Adverse Events (AE) version 4.0 induced by these drugs.
- execution of a CT scan no earlier than 4 weeks before enrollment
- good or intermediate prognostic assessment (according to criteria of the prognostic system of the International Metastatic RCC Database Consortium)
Key exclusion criteria (11 listed)
- another known cause of diarrhea (e.g. infectious gastroenteritis. Clostridium difficile infection, celiac disease, inflammatory bowel disease, irritable bowel syndrome, chronic pancreatitis, biliary salt diarrhea)
- previous colorectal surgery or cutaneous stoma
- food allergies
- recent (<6 weeks) therapy with drugs that could possibly alter gut microbiota (e.g. antibiotics, probiotics, proton pump inhibitors, immunosuppressants, metformin)
- another cancer (except for surgically treated basocellular carcinoma)
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 |
|---|---|---|
| Donor FMTFecal microbiota transplantation using stools from healthy donors | Other | Donor FMT |
| Sham FMTSham fecal microbiota transplantation | Other | Sham FMT |
Primary outcome
rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments
Time frame: 4 weeks
rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments
8 secondary outcomes
rate of patients who need to stop or reduce treatment with tyrosine-kinase inhibitors
Time frame: 4 weeks
rate of patients who experience resolution of diarrhea 1 week after the end of treatments
Time frame: 1 week
rate of patients who experience resolution of diarrhea 2 weeks after the end of treatments
Time frame: 2 weeks
rate of patients who experience resolution of diarrhea 8 weeks after the end of treatments
Time frame: 8 weeks
rate of patients who experience decrease of diarrhea until grade G1 or lower 1 week after the end of treatments
Time frame: 1 week
rate of patients who experience decrease of diarrhea until grade G1 or lower 2 weeks after the end of treatments
Time frame: 2 weeks
rate of patients who experience decrease of diarrhea until grade G1 or lower 4 weeks after the end of treatments
Time frame: 4 weeks
rate of patients who experience decrease of diarrhea until grade G1 or lower 8 weeks after the end of treatments
Time frame: 8 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 17 Mar 2020.
- Derived from this study: PubMed 32859933Ianiro G, Rossi E, Thomas AM, Schinzari G, Masucci L, Quaranta G, Settanni CR, Lopetuso LR, Armanini F, Blanco-Miguez A, Asnicar F, Consolandi C, Iacovelli R, Sanguinetti M, Tortora G, Gasbarrini A, Segata N, Cammarota G. Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma. Nat Commun. 2020 Aug 28;11(1):4333. doi: 10.1038/s41467-020-18127-y.
- Individual participant dataSharing planned: No
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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 Donor FMT in people with Diarrhea Caused by Drug (Disorder) and Renal Cell Cancer, run by Catholic University of the Sacred Heart at 1 site in Italy.
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 8 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 17 Mar 2020. 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 Italy. 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 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?
rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04040712, which also lists 1 linked publication.
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 17 Mar 2020.