Overview

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.

Eligibility

Inclusion Criteria:

1. Written informed consent to study procedures;
2. Male or female, age > 18 years (at the time consent is obtained);
3. Histological or cytological documentation of HNSCC that was diagnosed as recurrent or metastatic and considered incurable by local therapies;
4. Indication to be treated with ICIs monotherapy, either pembrolizumab or nivolumab or in combination with chemotherapy, according to standard clinical practice;
5. ECOG Performance PS score < 2;
6. Adequate kidney, liver and bone marrow function;
7. Will and ability to comply with the protocol.

Exclusion Criteria:

1. Disease that is suitable for local therapy administered with curative intent;
2. Prior therapy with anti-PD-1 or anti-PD-L1 agents;
3. History of severe allergic reactions or hypersensitivity to trial drugs or any of their excipients;
4. Major surgery < 28 days prior to receiving the first dose of study medication;
5. 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;
6. 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.
7. 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.
8. 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.
9. 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.
10. Diagnosis of current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents;
11. Diagnosis of active infection that required systemic antibiotics therapy, orally or intravenous;.
12. 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.
13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness;
14. Any serious and/or unstable medical conditions, psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
15. Receipt of any live vaccine within 30 days of planned start of study therapy.
16. 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.