Assessment of Swallowing Function and Quality of Life in Oropharyngeal Cancer Patients Treated by Chemo-radiotherapy

Patient Reported Outcomes in Term of Swallowing and Quality of Life After Prophylactic Versus Reactive Percutaneous Endoscopic Gastrostomy Tube Placement in Advanced Oropharyngeal Cancer Patients Treated With Definitive Chemo-radiotherapy

Open-label, interventional, multicentric, randomized, phase III study. Cancer studied is the oropharyngeal cancer.

Study is composed by 2 arms of subjects: prophylactic or reactive percutaneous endoscopic gastrostomy tube placement.

All subjects will be treated with a cisplatin standard chemotherapy regimen and by simultaneous integrated boost (SIB) intensity modulated radiotherapy (IMRT).

Open-label, interventional, multicentric, randomized, phase III study. Cancer studied is the oropharyngeal cancer.

Study is composed by 2 arms of subjects (male or female): prophylactic or reactive percutaneous endoscopic gastrostomy tube placement.

The arm will be allocated by randomisation (1:1).

• Prophylactic PEG (pPEG): Prophylactic PEG tube will be placed before the start of the study treatment (CRT). The enteral nutrition will start following the assessment by the clinical dietitian in order to complete the current oral consumption according to the estimated energy needs (on the basis of 30 to 35 kcal / kg adapted and 1.2 to 1.5 g / prot./ kg.BW) with an increase as needed during the treatment.
• Reactive PEG (rPEG): Reactive PEG tube will be placed and enteral nutrition initiated, during the study treatment period in case of decrease of oral intake less than 2/3 of estimated energy requirements (based on 30-35 kcal / adapted kg .BW and 1.2 - 1.5 g/prot./adapted kg. BW) for a period of or anticipated to be, greater than 7 days or weight loss ≥ 5% from pre-treatment baseline).

All subjects will be treated with a cisplatin standard chemotherapy regimen and by simultaneous integrated boost (SIB) intensity modulated radiotherapy (IMRT).

Cisplatin: Two therapeutic regimens are allowed:

• Days 1 and 22: cisplatin 100mg/m2 IV
• Days 1,8,15,22,29 and 39: weekly cisplatin 40mg/m2 IV

Radiotherapy: The median dose prescription will be 32 x 2.16 Gy to the high risk PTV and 32 x 1.75 Gy to the elective PTV.

Medical device: The medical device used in this trial is a percutaneous endoscopic gastrostomy tube with the CE label: CE0120. The medical device is used in the indication of the notice.

The estimated number of subjects to screen is 121 patients for an estimated number of 110 patients randomised for 100 evaluable patients.

The end of study will be declared when all the following criteria will have been met:

• The study ends after last visit of the last patient remaining in the study.
• The trial is mature for the analysis of the endpoints as defined in the protocol, if the trial reaches its endpoints.
• The database has been fully cleaned and frozen for all analyses.

Inclusion Criteria:

1. Age ≥ 18 years old

2. ECOG performance status ≤ 2

3. Female and Male

4. Newly diagnosed, histologically confirmed primary squamous cell carcinoma of the oropharynx

5. Candidate for curative intent radiotherapy and systemic treatment

6. No prior or current anticancer treatment for the HNSCC (e.g. neo-adjuvant chemotherapy, surgery)

7. Diagnosis biopsy results

8. HPV/p 16 testing results

9. Serum test (for subjects of childbearing potential) negative within 7 days prior to the 1st CRT administration.

10. Women of childbearing potential must agree to use of one highly effective method of contraception prior study entry, during the course of the study and at least 6 months after the last administration of cisplatin.

11. Men with childbearing potential partner must agree to use condom during the course of this study and for at least 6 months after the last administration of the cisplatin.

12. Adequate bone marrow function as defined below:

    • Absolute neutrophil count (ANC) ≥1500/µL or 1.5x109/L
    • Hemoglobin ≥ 9 g/dL
    • Platelets ≥100000/µL or 100x109/L

13. Adequate liver function as defined below:

    • Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome < 3 x UNL is allowed
    • AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN
    • Alkaline phosphatase ≤ 2.5 x ULN

14. Adequate renal function as defined below:

    • Creatinine ≤ 1.5 x UNL and creatinine clearance > 60 mL/min

15. Peripheral neuropathy ≤ grade 1

16. Hear impaired ≤ grade 1

17. Completion of all necessary screening procedures within 15 days prior to randomisation.

18. Signed Informed Consent form (ICF) obtained prior to any study related procedure.

19. Ability to understand and complete the questionnaires (language proficiency, cognitive functioning) as judged by principal investigator upon screening

Exclusion Criteria:

1. Severe malnutrition
2. Dysphagia requiring a liquid or puree texture modified diet (grade ≥ 2 (CTCAE_v.5)
3. Distant metastasis
4. Serious coagulation disorders (INR>1.5, PTT>50s, platelets <50000/mm3)
5. Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
6. Other malignancies in the 3 years prior to study entry except of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin;
7. Pregnant and/or lactating women.
8. Known hypersensitivity to the study drug (cisplatin) or excipients.