PEctin Rapid Fentanyl Efficacy Clinical Trial For pAin at Swallowing Undergoing radioTherapy

Study Overview
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Brief Summary
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The primary objective of the present phase IIIb study is to assess the efficacy of FPNS compared with Physician Choice-Usual Care (PC-UC) in the reduction of swallowing predictable BTP in head and neck cancer patients undergoing radiotherapy with or without chemotherapy.

Detailed Description
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Population: In and out patients with head and neck cancer undergoing radiotherapy, regardless of the day of the radiotherapy treatment, with or without chemotherapy and taking at least 60 mg of oral morphine daily or an equianalgesic dose of another opioid to control background pain (background pain controlled is defined as NRS <4) but with uncontrolled pain at swallowing (moderate/severe intensity: ≥ 4 on a NRS 0-10). Study design: Patients that have signed the ICF and met inclusion and exclusion criteria are randomly assigned 1:1 to receive one of the following predictable BTP at swallowing treatments: Fentanyl pectin nasal spray (FPNS) Physician choice-Usual Care (PC-UC) Each patient will take the drug no more than 3 episode a day (at main meals: breakfast, lunch and dinner) for 15 episodes in total in 6 (-1, +2) consecutive days. At each episode the patients will record the pain at baseline (before drug administration), and 10, 20 30 minutes after taking FPNS or PC-UC. At each meal, if the administered dose of FPNS or PC-UC is not adequately effective on pain control, the patient is allowed to take a rescue medication of IRMS after 30 min from FPNS or PC-UC administration.

Official Title
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Multicenter Randomized Open Trial to Evaluate Efficacy of Fentanyl Pectin Nasal Spray vs Physician Choice-Usual Care in Reducing Predictable Breakthrough Pain at Swallowing in Head/Neck Cancer Patients Undergoing Radiotherapy

Conditions
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Predictable BTP at Swallowing in in Head/Neck Cancer Patients Undergoing Radiotherapy Already Receiving Opioid Therapy for Background Pain

Intervention / Treatment
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* Drug: Fentanyl pectin nasal spray (FPNS)
* Drug: Physician choice-Usual care (PC-UC)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male and female aged 18 years or over Diagnosis of stage III-IV cancer of oral cavity, oropharynx, hypopharynx, larynx, salivary glands Receiving radiation therapy (RT) with or without concurrent platinum based chemotherapy or cetuximab as first line treatment or as postoperative adjuvant treatment Background pain controlled with at least 60 mg oral morphine daily or an equianalgesic dose of another opioid. A background pain controlled is defined as NRS <4 Uncontrolled pain during swallowing (predictable BTP at swallowing) with an intensity ≥4 on an 11-point numeric scale (0=no pain; 10=worst possible pain). This pain will have to be measured with the ingestion of a solid/liquid food (depending on the ability to swallow or less solid foods of the patient at moment) Patients able to receive a nasal spray therapy Willing and able to sign an informed consent form Females with childbearing potential must provide a negative pregnancy test and both males and females must be using adequate contraception during the study Patients with PEG or jejunostomy, if are available to take by mouth meals (solid or liquid) or just liquid in order to be compliant with the protocol. Exclusion Criteria: Patients with known metastatic disease Known hypersensitivity to opioids, to Fentanyl or to drugs used in the PC-UC, and/or to study medications' formulation ingredients Patients with impaired chemistry laboratory exams, assessed as routine clinical practice before radiotherapy start: a. Hepatic function: i. Total bilirubin > 2 times the upper-normal limit (ULN) ii. Serum transaminase > 5 times ULN b. Renal function: i. Serum creatinine concentration > 2 times ULN Pregnant or breastfeeding women Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study Patients planned to receive other investigational treatments during study period Patients with moderate to severe respiratory impairment Patients with nasogastric feeding tube Patients that cannot take FPNS according to investigator's judgment

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PecFent nasal spray<br>Patients that have signed the ICF and met inclusion and exclusion criteria are randomly assigned 1:1 to receive one of the following IP-BTP treatments: Fentanyl pectin nasal spray (FPNS) Physician choice-Usual Care (PC-UC) | Drug: Fentanyl pectin nasal spray (FPNS)<br>* The first dose of FPNS will be 100 mcg dose. It will be increased until 800 mcg dose.<br>|
| Active Comparator: Physician choice-Usual Care (PC-UC)<br>Patients that have signed the ICF and met inclusion and exclusion criteria are randomly assigned 1:1 to receive one of the following IP-BTP treatments: Fentanyl pectin nasal spray (FPNS) Physician choice-Usual Care (PC-UC) | Drug: Physician choice-Usual care (PC-UC)<br>* The PC-UC will be started at a dose according to the physician choice. If this dose of PC-UC is effective on pain control, at the following meal the patient will take the same dose of PC-UC. If the dose of PC-UC results non effective on pain control, at the following meal the patient will take an increased dose of the same PC-UC drug or change the PC-UC drug, according to the physician choice.<br>* Other names: PC-UC is any drug used in clinical use for treating IP-BTP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the mean intensity of predictable BTP at swallowing from the baseline to 20 minutes after taking FPNS/PC-UC (PID20). |  | up to 6 (-1,+2) days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in the mean intensity of predictable BTP at swallowing from the baseline to 10 and 30 minutes after taking FPNS/PC-UC. |  | up to 6 (-1,+2) days | 
| Time to reach the maximal pain reduction after administration of FPNS/PC-UC (evaluation of reduction in pain intensity score at each time point: 10,20,30 min after administration of FPNS or PC-UC) |  | up to 6 (-1,+2) days | 
| Patient's swallowing pain relief will be measured at the end of the study period through the 5-points numeric scale (0=none; 4=complete). |  | end of study | 
| Clinically meaningful pain reduction will be analyzed by assessing percentages of episodes with ≥ 2 point reductions after drug treatment versus baseline and after FPNS versus PC-UC |  | up to 6 (-1,+2) days | 
| Administration of rescue medication (dose and frequency) |  | up to 6 (-1,+2) days | 
| Patient's dysphagia assessment. An evaluation of dysphagia by MDADI questionnaire will be performed at baseline and at the end of the study period. |  | day 1 and end of study | 
| Safety and tolerability |  | up to 6 (-1,+2) days |