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The Effect of Prebiotic Inulin on Patients Affected by R/M HNSCC Treated With Immune Checkpoint Inhibitors (PRINCESS)

Primary Purpose

Head and Neck Squamous Cell Carcinoma

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
inulin
Pembrolizumab
Nivolumab
Sponsored by
Fondazione del Piemonte per l'Oncologia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma focused on measuring microbiome, inulin, Immune Checkpoint Inhibitors, chemotherapy, cytokines, immune cells, HNSCC, Recurrent/Metastatic, Head and Neck Squamous Cell Carcinoma, Carcinoma, Head and Neck Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Written informed consent to study procedures; Male or female, age > 18 years (at the time consent is obtained); Histological or cytological documentation of HNSCC that was diagnosed as recurrent or metastatic and considered incurable by local therapies; Indication to be treated with ICIs monotherapy, either pembrolizumab or nivolumab or in combination with chemotherapy, according to standard clinical practice; ECOG Performance PS score < 2; Adequate kidney, liver and bone marrow function; Will and ability to comply with the protocol. Exclusion Criteria: Disease that is suitable for local therapy administered with curative intent; Prior therapy with anti-PD-1 or anti-PD-L1 agents; History of severe allergic reactions or hypersensitivity to trial drugs or any of their excipients; Major surgery < 28 days prior to receiving the first dose of study medication; Toxicity from previous anticancer treatment that includes: Grade 3/4 toxicity considered related to prior therapy and that led to treatment discontinuation; toxicity related to prior treatment that has not resolved to > Grade 1; Central nervous system (CNS) metastases and/or carcinomatous meningitis; with the following exception: patients with asymptomatic CNS metastases who are clinically stable and have no requirement for steroids for at least 14 days prior to the first dose of trial treatment. Patients with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability. Other additional malignancies that are progressing or require active treatment within the last 5 years with the exception of localized basal and squamous cell carcinoma of the skin or cervical cancer in situ. Active autoimmune disease or syndrome that required systemic treatment within the past 2 years (with use of corticosteroids or immunosuppressive drugs). Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Systemic steroid therapy (≥10 mg oral prednisone per day or equivalent) or other immunosuppressive agents within 7 days prior to the first dose of trial treatment. Diagnosis of current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents; Diagnosis of active infection that required systemic antibiotics therapy, orally or intravenous;. Clinically significant cardiovascular disease within the 6 months prior to the first dose of trial treatment with a New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF); symptomatic pericarditis. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness; Any serious and/or unstable medical conditions, psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial Receipt of any live vaccine within 30 days of planned start of study therapy. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.

Sites / Locations

  • Fondazione del Piemonte per l'Oncologia-IRCCS CandioloRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A

Arm B

Arm Description

Pembrolizumab in monotherapy or in combination with chemotherapy (platinum + 5 FU) in standard clinical practice according to the international and local guidelines + inulin

Nivolumab in monotherapy or in combination with chemotherapy (platinum + 5 FU) in standard clinical practice according to the international and local guidelines + inulin

Outcomes

Primary Outcome Measures

Alpha diversity and Beta diversity analysis in the Gut Microbiota
Comparison of gut microbiota diversity with Shannon index in faeces samples. The analyses were conducted using QIIME software
Evaluation of circulating cytokines dynamics
Analysis of multiple cytokines for identify a cytokine signature related to a patient's outcome and be able to recognize patients who will benefit from treatment. Plasma Levels of 18 Cytokines TGF-, TNF-, VEGF, INF-, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, CCL-2, CCL4, CCL-22, and CXCL-10 were evaluated with the Ella Simple Plex system (ProteinSimple™, San Jose, CA, USA)The concentrations were expressed in pg/mL. IL-21 was assessed with the ELISA method (R & D System, Minneapolis, MN, USA). The measured optical densities were expressed as pg/mL.
Rate and evaluation of modification of circulating immune-phenotype dynamics
Rate and evaluation of modification of main circulating immune characters as T lymphocytes, B Lymphocytes, Tregs, neutrophils, Natural Killer, NKT, MDSC during study combination treatment
Evaluation of Immune-predictive molecules
Evaluation of immunomodulatory molecules (PD-1; PD-L1/2; HLA- E; TIM3; LAG3; OX40; VISTA; ICOS) will be assessed at each established time point
Overall Survival Rate
OS and the correlation with GM diversity and circulating cytokines and immune cells dynamics.

Secondary Outcome Measures

Full Information

First Posted
January 31, 2023
Last Updated
April 7, 2023
Sponsor
Fondazione del Piemonte per l'Oncologia
Collaborators
Ospedale Santa Croce-Carle Cuneo, Università degli Studi di Trento
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1. Study Identification

Unique Protocol Identification Number
NCT05821751
Brief Title
The Effect of Prebiotic Inulin on Patients Affected by R/M HNSCC Treated With Immune Checkpoint Inhibitors
Acronym
PRINCESS
Official Title
The Effect of Prebiotic Inulin on Patients Affected by Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) Treated With Immune Checkpoint Inhibitors (ICIs): Princess Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 2, 2021 (Actual)
Primary Completion Date
December 2, 2024 (Anticipated)
Study Completion Date
December 2, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione del Piemonte per l'Oncologia
Collaborators
Ospedale Santa Croce-Carle Cuneo, Università degli Studi di Trento

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The PRINCESS study is a hypothesis-generating, interventional, open-label, non pharmacological trial designed to characterize the translational and clinical implications of the regular assumptions of inulin on Gut Microbiota, circulating cytokines and immune cells dynamics during ICIs +/- chemotherapy on patients affected by R/M HNSCC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Squamous Cell Carcinoma
Keywords
microbiome, inulin, Immune Checkpoint Inhibitors, chemotherapy, cytokines, immune cells, HNSCC, Recurrent/Metastatic, Head and Neck Squamous Cell Carcinoma, Carcinoma, Head and Neck Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Pembrolizumab in monotherapy or in combination with chemotherapy (platinum + 5 FU) in standard clinical practice according to the international and local guidelines + inulin
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Nivolumab in monotherapy or in combination with chemotherapy (platinum + 5 FU) in standard clinical practice according to the international and local guidelines + inulin
Intervention Type
Dietary Supplement
Intervention Name(s)
inulin
Intervention Description
Inulin will be given to enrolled patients according to manufacturer label indications. ICIs (i.e. nivolumab and pembrolizumab) alone or in combination with chemotherapy, if clinically indicated, and their administration scheduling will be planned as per international and local guidelines.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Pembrolizumab in monotherapy or in combination with chemotherapy (platinum + 5 FU) in standard clinical practice according to the international and local guidelines + inulin
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Intervention Description
Nivolumab in monotherapy or in combination with chemotherapy (platinum + 5 FU) in standard clinical practice according to the international and local guidelines + inulin
Primary Outcome Measure Information:
Title
Alpha diversity and Beta diversity analysis in the Gut Microbiota
Description
Comparison of gut microbiota diversity with Shannon index in faeces samples. The analyses were conducted using QIIME software
Time Frame
12 month
Title
Evaluation of circulating cytokines dynamics
Description
Analysis of multiple cytokines for identify a cytokine signature related to a patient's outcome and be able to recognize patients who will benefit from treatment. Plasma Levels of 18 Cytokines TGF-, TNF-, VEGF, INF-, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, CCL-2, CCL4, CCL-22, and CXCL-10 were evaluated with the Ella Simple Plex system (ProteinSimple™, San Jose, CA, USA)The concentrations were expressed in pg/mL. IL-21 was assessed with the ELISA method (R & D System, Minneapolis, MN, USA). The measured optical densities were expressed as pg/mL.
Time Frame
12 month
Title
Rate and evaluation of modification of circulating immune-phenotype dynamics
Description
Rate and evaluation of modification of main circulating immune characters as T lymphocytes, B Lymphocytes, Tregs, neutrophils, Natural Killer, NKT, MDSC during study combination treatment
Time Frame
12 month
Title
Evaluation of Immune-predictive molecules
Description
Evaluation of immunomodulatory molecules (PD-1; PD-L1/2; HLA- E; TIM3; LAG3; OX40; VISTA; ICOS) will be assessed at each established time point
Time Frame
12 month
Title
Overall Survival Rate
Description
OS and the correlation with GM diversity and circulating cytokines and immune cells dynamics.
Time Frame
through study completion, an average of 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent to study procedures; Male or female, age > 18 years (at the time consent is obtained); Histological or cytological documentation of HNSCC that was diagnosed as recurrent or metastatic and considered incurable by local therapies; Indication to be treated with ICIs monotherapy, either pembrolizumab or nivolumab or in combination with chemotherapy, according to standard clinical practice; ECOG Performance PS score < 2; Adequate kidney, liver and bone marrow function; Will and ability to comply with the protocol. Exclusion Criteria: Disease that is suitable for local therapy administered with curative intent; Prior therapy with anti-PD-1 or anti-PD-L1 agents; History of severe allergic reactions or hypersensitivity to trial drugs or any of their excipients; Major surgery < 28 days prior to receiving the first dose of study medication; Toxicity from previous anticancer treatment that includes: Grade 3/4 toxicity considered related to prior therapy and that led to treatment discontinuation; toxicity related to prior treatment that has not resolved to > Grade 1; Central nervous system (CNS) metastases and/or carcinomatous meningitis; with the following exception: patients with asymptomatic CNS metastases who are clinically stable and have no requirement for steroids for at least 14 days prior to the first dose of trial treatment. Patients with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability. Other additional malignancies that are progressing or require active treatment within the last 5 years with the exception of localized basal and squamous cell carcinoma of the skin or cervical cancer in situ. Active autoimmune disease or syndrome that required systemic treatment within the past 2 years (with use of corticosteroids or immunosuppressive drugs). Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Systemic steroid therapy (≥10 mg oral prednisone per day or equivalent) or other immunosuppressive agents within 7 days prior to the first dose of trial treatment. Diagnosis of current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents; Diagnosis of active infection that required systemic antibiotics therapy, orally or intravenous;. Clinically significant cardiovascular disease within the 6 months prior to the first dose of trial treatment with a New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF); symptomatic pericarditis. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness; Any serious and/or unstable medical conditions, psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial Receipt of any live vaccine within 30 days of planned start of study therapy. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Danilo Galizia
Phone
+39 011 993 3250
Email
danilo.galizia@ircc.it
First Name & Middle Initial & Last Name or Official Title & Degree
Marco Merlano
Phone
+39 011 993 3250
Email
marcocarlo.merlano@ircc.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Danilo Galizia
Organizational Affiliation
FPO IRCCS Candiolo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fondazione del Piemonte per l'Oncologia-IRCCS Candiolo
City
Candiolo
State/Province
Turin
ZIP/Postal Code
10060
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Annamaria Nuzzo, PhD
Phone
+390119933398
Email
annamaria.nuzzo@ircc.it
First Name & Middle Initial & Last Name & Degree
Danilo Galizia, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

The Effect of Prebiotic Inulin on Patients Affected by R/M HNSCC Treated With Immune Checkpoint Inhibitors

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