NCT05821751

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Dec 2021

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 2, 2021

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

January 31, 2023

Completed
3 months until next milestone

First Posted

Study publicly available on registry

April 20, 2023

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 2, 2024

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 2, 2025

Completed
Last Updated

April 20, 2023

Status Verified

April 1, 2023

Enrollment Period

3 years

First QC Date

January 31, 2023

Last Update Submit

April 7, 2023

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

microbiomeinulinImmune Checkpoint Inhibitorschemotherapycytokinesimmune cellsHNSCCRecurrent/MetastaticHead and Neck Squamous Cell CarcinomaCarcinomaHead and Neck Carcinoma

Outcome Measures

Primary Outcomes (5)

  • 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

    12 month

  • 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.

    12 month

  • 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

    12 month

  • 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

    12 month

  • Overall Survival Rate

    OS and the correlation with GM diversity and circulating cytokines and immune cells dynamics.

    through study completion, an average of 1 year

Study Arms (2)

Arm A

EXPERIMENTAL

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

Dietary Supplement: inulinDrug: Pembrolizumab

Arm B

EXPERIMENTAL

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

Dietary Supplement: inulinDrug: Nivolumab

Interventions

inulinDIETARY_SUPPLEMENT

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.

Arm AArm B
PembrolizumabDRUG

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

Arm A
NivolumabDRUG

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

Arm B

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fondazione del Piemonte per l'Oncologia-IRCCS Candiolo

Candiolo, Turin, 10060, Italy

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and NeckNeoplasm MetastasisCarcinoma

Interventions

InulinpembrolizumabNivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous CellNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsHead and Neck NeoplasmsNeoplasms by SiteNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

StarchGlucansBiopolymersPolymersMacromolecular SubstancesDietary CarbohydratesCarbohydratesFructansPolysaccharidesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Danilo Galizia

    FPO IRCCS Candiolo

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Danilo Galizia

CONTACT

+39 011 993 3250danilo.galizia@ircc.it

Marco Merlano

CONTACT

+39 011 993 3250marcocarlo.merlano@ircc.it

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 31, 2023

First Posted

April 20, 2023

Study Start

December 2, 2021

Primary Completion

December 2, 2024

Study Completion

December 2, 2025

Last Updated

April 20, 2023

Record last verified: 2023-04

Data Sharing

IPD Sharing
Will share

Locations

IT(1)