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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Oropharyngeal Cancer

Intervention / Treatment
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* Device: Percutaneous Endoscopic Gastrotomy tube placement
* Drug: Cisplatin injection
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old ECOG performance status ≤ 2 Female and Male Newly diagnosed, histologically confirmed primary squamous cell carcinoma of the oropharynx Candidate for curative intent radiotherapy and systemic treatment No prior or current anticancer treatment for the HNSCC (e.g. neo-adjuvant chemotherapy, surgery) Diagnosis biopsy results HPV/p 16 testing results Serum test (for subjects of childbearing potential) negative within 7 days prior to the 1st CRT administration. 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. 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. 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 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 Adequate renal function as defined below: Creatinine ≤ 1.5 x UNL and creatinine clearance > 60 mL/min Peripheral neuropathy ≤ grade 1 Hear impaired ≤ grade 1 Completion of all necessary screening procedures within 15 days prior to randomisation. Signed Informed Consent form (ICF) obtained prior to any study related procedure. Ability to understand and complete the questionnaires (language proficiency, cognitive functioning) as judged by principal investigator upon screening Exclusion Criteria: Severe malnutrition Dysphagia requiring a liquid or puree texture modified diet (grade ≥ 2 (CTCAE_v.5) Distant metastasis Serious coagulation disorders (INR>1.5, PTT>50s, platelets <50000/mm3) 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. 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; Pregnant and/or lactating women. Known hypersensitivity to the study drug (cisplatin) or excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label, randomized study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prophylactic PEG<br>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. | Device: Percutaneous Endoscopic Gastrotomy tube placement<br>* placement of the PEG tube depends on arm<br>Drug: Cisplatin injection<br>* Two therapeutic regimen allowed: Days 1 and 22 : cisplatin 100mg/m2 IV Days 1,8,15,22,29,36: weekly cisplatin 40 mg/m2 IV<br>Radiation: Radiotherapy<br>* Simultaneous integrated boost (SIB) intensity modulated radiotherapy (IMRT). 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.<br>|
| Experimental: Reactive PEG<br>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). | Device: Percutaneous Endoscopic Gastrotomy tube placement<br>* placement of the PEG tube depends on arm<br>Drug: Cisplatin injection<br>* Two therapeutic regimen allowed: Days 1 and 22 : cisplatin 100mg/m2 IV Days 1,8,15,22,29,36: weekly cisplatin 40 mg/m2 IV<br>Radiation: Radiotherapy<br>* Simultaneous integrated boost (SIB) intensity modulated radiotherapy (IMRT). 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| global M.D. Anderson Dysphagia Inventory score at 6 months after end of treatment. | The M.D.Anderson Dysphagia inventory is a dysphagia-specific quality-of-life questionnaire for patients with H&N cancer including 20 items divided into 4 subscales emotional (6 questions), functional (5 questions), physical (8 questions) and one global question. Each subscale has a score ranging from 1 to 5 (higher scores represent a better outcome). The mean score of the 20 items will be multiplied by a factor of 20 to obtain a MDADI total score which ranges from 20 (extremely low functioning) to 100 (high functioning). A difference of 8 points in MDADI score is considered as the Minimal Clinically Important Difference for the trial. | at 6 months after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Quality of Life | Outcome measure: completion of EORTC QLQ-C30 questionnaire | Baseline; at week 3 & 6 during treatment; at 1,3, 6, 12 and 24 months after end of treatment | 
| Assessment of Quality of Life | Outcome measure: completion of EORTC QLQ-H&N43 module questionnaire | Baseline; at week 3 & 6 during treatment; at 1,3, 6, 12 and 24 months after end of treatment | 
| Assessment of Quality of Life | Outcome measure: completion of FACT-HN questionnaire | Baseline; at week 3 & 6 during treatment; at 1,3, 6, 12 and 24 months after end of treatment | 
| Assessment of chemo-radiotherapy treatment related toxicities and PEG tube placement complications | Outcome measure: Incidence, type and severity of all adverse events (AEs) and serious adverse events according to CTCAE version 5.0 ; | through study completion, an average of 38 months | 
| Assessment of chemo-radiotherapy treatment related toxicities and PEG tube placement complications | Outcome measure:Incidence, type and severity of radiotherapy related AEs also according to Radiation Therapy Oncology Group (RTOG) / European Organisation for Research and treatment of Cancer (EORTC) scores; In the RTOG/EORTC Late Radiation Morbidity Scoring, 0 means an absence of radiation effects and 5 means the effects led to death. The severity of reactions is graded from 1 through 4. | through study completion, an average of 38 months | 
| Assessment of chemo-radiotherapy treatment related toxicities and PEG tube placement complications | Outcome measure:Severity of oropharyngeal mucositis and swallowing disorders according to Internal consensus scale (ICS); | through study completion, an average of 38 months | 
| Assessment of chemo-radiotherapy treatment related toxicities and PEG tube placement complications | Outcome measure: Oropharyngeal mucositis according to the oral mucositis weekly questionnaire-Head and Neck cancer (OMWQ-NH) completed by the subject; | through study completion, an average of 38 months | 
| Assessment of chemo-radiotherapy treatment related toxicities and PEG tube placement complications | Outcome measure: Salivary toxicity according to the xerostomia questionnaire completed by the subject. | through study completion, an average of 38 months | 
| Impact of the nutritional status on survival and toxicity outcomes | Outcome measure: Clinical dietitian assessment including risk screening by Nutritional Risk Screening 2002 (NRS-2002) | Baseline, during treatment period (7 weeks) and follow-up period (24 months) | 
| Impact of the nutritional status on survival and toxicity outcomes | Outcome measure: Clinical dietitian assessment using GLIM criteria (Global Leadership Initiative on Malnutrition criteria). | Baseline, during treatment period (7 weeks) and follow-up period (24 months) | 
| Assessment of clinical tumour response after study treatment | Outcome measure:Tumour response after study treatment measured by DECT and PET-CT | at 3 and 12 months after end of treatment | 
| Assessment of the subject outcome | Outcome measure: loco regional control (LRC) | at 3, 12 and 36 months after end of treatment | 
| Assessment of the subject outcome | Outcome measure: distant recurrence/distant progression (DR/DP) | at 3, 12 and 36 months after end of treatment | 
| Assessment of the subject outcome | Outcome measure: second primary (SP) | at 3, 12 and 36 months after end of treatment | 
| Assessment of the subject outcome | Outcome measure: disease-free survival (DFS) | at 3, 12 and 36 months after end of treatment | 
| Assessment of the subject outcome | Outcome measure: disease specific survival (DSS) | at 3, 12 and 36 months after end of treatment | 
| Assessment of the subject outcome | Outcome measure: overall survival (OS) | at 3, 12 and 36 months after end of treatment | 
| Impact of tobacco consumption on the outcomes | Outcome measure: Assessment of the smoking consumption | Baseline, at week 3 and at 1, 3, 6, 12 and 24 months after the end of treatment. | 
| Impact of HPV on the outcomes | Outcome measure: HPV/p16 status | at screening | 
| Cost-Effectiveness of each treatment strategy | Outcome measure: EuroQol 5D5L Questionnaire | during the pre-study treatment period (within 15 days after randomisation and before starting study treatment) and at 12 months after end of treatment | 
| Clinical validation of cancer prediction models available at www.predictcancer.org | HPV-based prognostic nomogram for oro-pharyngeal carcinoma | at 6 months after treatment | 
| Clinical validation of cancer prediction models available at www.predictcancer.org | prediction tool for swallowing dysfunction, xerostomia, sticky saliva and tube feeding dependence | at 6 months after treatment |