Ignite Creation Date:
2024-05-06 @ 12:53 PM
Last Modification Date:
2024-10-26 @ 1:05 PM
Study NCT ID:
NCT03870607
Status:
RECRUITING
Last Update Posted:
2023-01-17
First Post:
2019-02-12
Brief Title:
Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy SCC of the Anal Canal BISQUIT
Sponsor:
AC Camargo Cancer Center
Organization:
AC Camargo Cancer Center
Study Overview
Official Title:
A Randomized Phase II Study of the Administration of Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy for Patients With Squamous Cell Carcinoma of the Anal Canal BISQUIT
Status:
RECRUITING
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BISQUIT
Brief Summary:
Phase II randomized study of the use of pre-and probiotics during the definitive treatment of chemotherapy-radiotherapy Ch-RT for patients with localized anal canal squamous cell cancer ACSCC with the objective of increasing the effectiveness of conventional treatment based on the assumptions of that there is a need for research that increases the cure rates of the definitive treatment of Ch-RT in the ACSCC ACSCC is a virus-associated tumor in many cases and therefore potentially immunogenic immunotherapy is a promising strategy in ACSCC and that pre- and probiotics can stimulate the immune system through modulation of the intestinal microbiota and improve oncological outcomes
Detailed Description:
Although anal canal squamous cell carcinoma ACSCC is rare in developed countries it has shown an annual increase of 4 in its incidence in Brazil and according to data from the Oncocenter Foundation of São Paulo FOSP 2338 cases were diagnosed in 2000 and 2016
The standard treatment for localized ACSCC without distant metastases is definitive chemo-radiotherapy Ch-RT concomitant with administration of a fluoropyrimidine 5FU or capecitabine combined with mitomycin or cisplatin which provides cure rates of 60-80 depending on the staging When there is no complete remission surgical rescue through anal amputation is the only potentially curative modality However this strategy is associated with great morbidity besides negative emotional and social impacts with consequent reduction of quality of life Therefore interventions that may increase the chance of cure in ACSCC should be investigated
The main risk factors for ACSCC are human papillomavirus HPV infections and immunosuppression including human immunodeficiency virus HIV infection Chronic HPV infection and HIV-induced immunosuppression point to research strategies that strengthen the immune system to reduce the risk of developing ACSCC In the metastatic setting the use of immune checkpoint inhibitors such as anti-programmed death protein-1 PD1 antibodies were shown to be promising in ACSCC patients promoting response rates of approximately 25 However there is no evidence of modulation interventions of the immune system in patients with localized ACSCC
Recently studies have shown that the composition of the intestinal microbiota influences the onset of colorectal cancer and may even disrupt the effects of chemotherapy in this neoplasm A preclinical study in animal model showed that E coli impaired the antitumor effect of fluoropyrimidines drug used in colorectal cancer and ACSCC The intestinal microbiota also participates in a large set of metabolic processes such as reduction hydrolysis dehydroxylation etc involved in drug metabolism For example some intestinal bacteria have β-glucuronidases that cleave glucuronide from the inactive metabolite of irinotecan SN-38G a drug used in gastrointestinal tumors releasing active metabolite SN38 in the intestine causing diarrhea and colitis Ciprofloxacin has been shown to inhibit this enzyme by suppressing the diarrhea associated with irinotecan in an experimental model of mice Mycoplasma hyorhinis encodes a thymidine phosphorylase that strongly restricts the cytostatic activity of pyrimidine nucleoside analogues
On the other hand the replacement of the intestinal microbiota carcinogenic Fusobacterium spp and Bacteriodes fragilis by a protective microbiota Bifidobacterium and Lactobacillus has been the reason of numerous investigations with prebiotics and probiotics According to the International Scientific Association of Probiotics and Prebiotics probiotics are composed of living organisms which when administered promote health benefits such as antimicrobial action against intestinal pathogens modulation of the immune system reduction of cholesterol levels reduction of colitis and prevention of colorectal cancer Kefir is an example of probiotic Already prebiotics are inert ingredients that promote alteration in the composition or activity of the gastrointestinal microflora conferring health benefits Example of prebiotic is polysaccharide inulin Studies with these compounds have been conducted showing promising results A small placebo-controlled trial using B breve breve Yakut in children undergoing chemotherapy for a variety of neoplasms has shown that this group had fewer episodes of fever and less frequency of use of intravenous antibiotics compared to controls There are also studies that suggest that the alteration of the intestinal flora can increase the effectiveness of immunotherapy as a form of modulation of the immune system in several animal models of colorectal cancer In addition the use of this strategy could have a modulatory effect on local and systemic toxicity of the treatment possibly reducing the morbidity of the treatment as already suggested by studies in cervical carcinomas
Despite the strong scientific rationale there are no studies that have evaluated the use of probiotics or prebiotics in order to increase the effectiveness of conventional Ch-RT treatment in ACSCC Therefore based on the assumptions that there is a need for research that increases the cure rates of the definitive treatment of Ch-RT in ACSCC ACSCC is a virus-associated tumor in many cases and therefore potentially immunogenic immunotherapy is a promising strategy in ACSCC and that pre- and probiotics can stimulate the immune system through modulation of the intestinal microbiota and improve oncological outcomes the investigators propose a randomized phase II study of the use of pre-probiotics during definitive treatment of Ch-RT for patients with ACSCC located
The primary hypothesis of this study is that addition of pre- and probiotics increases the proportion of patients with complete clinical and radiological response after Ch-RT to ACSCC Secondary hypotheses are that pre- and probiotics increase the metabolic response measured by positron emission computed tomography PET-CT with 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose 18-FDG and promote greater control of local disease after Ch-RT and reduce local and systemic toxicity of treatment
The standard treatment for localized ACSCC without distant metastases is definitive chemo-radiotherapy Ch-RT concomitant with administration of a fluoropyrimidine 5FU or capecitabine combined with mitomycin or cisplatin which provides cure rates of 60-80 depending on the staging When there is no complete remission surgical rescue through anal amputation is the only potentially curative modality However this strategy is associated with great morbidity besides negative emotional and social impacts with consequent reduction of quality of life Therefore interventions that may increase the chance of cure in ACSCC should be investigated
The main risk factors for ACSCC are human papillomavirus HPV infections and immunosuppression including human immunodeficiency virus HIV infection Chronic HPV infection and HIV-induced immunosuppression point to research strategies that strengthen the immune system to reduce the risk of developing ACSCC In the metastatic setting the use of immune checkpoint inhibitors such as anti-programmed death protein-1 PD1 antibodies were shown to be promising in ACSCC patients promoting response rates of approximately 25 However there is no evidence of modulation interventions of the immune system in patients with localized ACSCC
Recently studies have shown that the composition of the intestinal microbiota influences the onset of colorectal cancer and may even disrupt the effects of chemotherapy in this neoplasm A preclinical study in animal model showed that E coli impaired the antitumor effect of fluoropyrimidines drug used in colorectal cancer and ACSCC The intestinal microbiota also participates in a large set of metabolic processes such as reduction hydrolysis dehydroxylation etc involved in drug metabolism For example some intestinal bacteria have β-glucuronidases that cleave glucuronide from the inactive metabolite of irinotecan SN-38G a drug used in gastrointestinal tumors releasing active metabolite SN38 in the intestine causing diarrhea and colitis Ciprofloxacin has been shown to inhibit this enzyme by suppressing the diarrhea associated with irinotecan in an experimental model of mice Mycoplasma hyorhinis encodes a thymidine phosphorylase that strongly restricts the cytostatic activity of pyrimidine nucleoside analogues
On the other hand the replacement of the intestinal microbiota carcinogenic Fusobacterium spp and Bacteriodes fragilis by a protective microbiota Bifidobacterium and Lactobacillus has been the reason of numerous investigations with prebiotics and probiotics According to the International Scientific Association of Probiotics and Prebiotics probiotics are composed of living organisms which when administered promote health benefits such as antimicrobial action against intestinal pathogens modulation of the immune system reduction of cholesterol levels reduction of colitis and prevention of colorectal cancer Kefir is an example of probiotic Already prebiotics are inert ingredients that promote alteration in the composition or activity of the gastrointestinal microflora conferring health benefits Example of prebiotic is polysaccharide inulin Studies with these compounds have been conducted showing promising results A small placebo-controlled trial using B breve breve Yakut in children undergoing chemotherapy for a variety of neoplasms has shown that this group had fewer episodes of fever and less frequency of use of intravenous antibiotics compared to controls There are also studies that suggest that the alteration of the intestinal flora can increase the effectiveness of immunotherapy as a form of modulation of the immune system in several animal models of colorectal cancer In addition the use of this strategy could have a modulatory effect on local and systemic toxicity of the treatment possibly reducing the morbidity of the treatment as already suggested by studies in cervical carcinomas
Despite the strong scientific rationale there are no studies that have evaluated the use of probiotics or prebiotics in order to increase the effectiveness of conventional Ch-RT treatment in ACSCC Therefore based on the assumptions that there is a need for research that increases the cure rates of the definitive treatment of Ch-RT in ACSCC ACSCC is a virus-associated tumor in many cases and therefore potentially immunogenic immunotherapy is a promising strategy in ACSCC and that pre- and probiotics can stimulate the immune system through modulation of the intestinal microbiota and improve oncological outcomes the investigators propose a randomized phase II study of the use of pre-probiotics during definitive treatment of Ch-RT for patients with ACSCC located
The primary hypothesis of this study is that addition of pre- and probiotics increases the proportion of patients with complete clinical and radiological response after Ch-RT to ACSCC Secondary hypotheses are that pre- and probiotics increase the metabolic response measured by positron emission computed tomography PET-CT with 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose 18-FDG and promote greater control of local disease after Ch-RT and reduce local and systemic toxicity of treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None