Clinical trial NCT01980498: PEctin Rapid Fentanyl Efficacy Clinical Trial For pAin at Swallowing Undergoing radioTherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Predictable BTP at Swallowing in in Head/Neck Cancer Patients Undergoing Radiotherapy Already Receiving Opioid Therapy for Background Pain
Lead sponsor: L.Molteni & C. dei F.lli Alitti-Soc. di Esercizio S.p.A.
Sponsor class: INDUSTRY
Collaborators: name: Consorzio Mario Negri Sud
First posted: 2013-11-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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:

1. Fentanyl pectin nasal spray (FPNS)
2. 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.

Eligibility criteria: Inclusion criteria:

1. Male and female aged 18 years or over
2. Diagnosis of stage III-IV cancer of oral cavity, oropharynx, hypopharynx, larynx, salivary glands
3. Receiving radiation therapy (RT) with or without concurrent platinum based chemotherapy or cetuximab as first line treatment or as postoperative adjuvant treatment
4. 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
5. 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)
6. Patients able to receive a nasal spray therapy
7. Willing and able to sign an informed consent form
8. Females with childbearing potential must provide a negative pregnancy test and both males and females must be using adequate contraception during the study
9. 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:

1. Patients with known metastatic disease
2. Known hypersensitivity to opioids, to Fentanyl or to drugs used in the PC-UC, and/or to study medications' formulation ingredients
3. 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
4. Pregnant or breastfeeding women
5. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study
6. Patients planned to receive other investigational treatments during study period
7. Patients with moderate to severe respiratory impairment
8. Patients with nasogastric feeding tube
9. Patients that cannot take FPNS according to investigator's judgment

Primary outcomes:
measure: Difference in the mean intensity of predictable BTP at swallowing from the baseline to 20 minutes after taking FPNS/PC-UC (PID20).
timeFrame: up to 6 (-1,+2) days
Secondary outcomes:
measure: The difference in the mean intensity of predictable BTP at swallowing from the baseline to 10 and 30 minutes after taking FPNS/PC-UC.
timeFrame: up to 6 (-1,+2) days
measure: 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)
timeFrame: up to 6 (-1,+2) days
measure: 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).
timeFrame: end of study
measure: 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
timeFrame: up to 6 (-1,+2) days
measure: Administration of rescue medication (dose and frequency)
timeFrame: up to 6 (-1,+2) days
measure: Patient's dysphagia assessment. An evaluation of dysphagia by MDADI questionnaire will be performed at baseline and at the end of the study period.
timeFrame: day 1 and end of study
measure: Safety and tolerability
timeFrame: up to 6 (-1,+2) days
Other outcomes:
Locations:
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)
state: Forlì - Cesena
city: Pesaro
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Marche Nord
state: Pesaro e Urbino
city: Candiolo
country: Italy
facility: Istituto per la Ricerca e la Cura del Cancro a carattere Scientifico - IRCC
state: Torino
city: Orbassano
country: Italy
facility: Azienda Ospedaliera San luigi di Gonzaga di Orbassano
state: Torino
city: Mirano
country: Italy
facility: Presidio Ospedaliero Mirano Azienda Ulss 13
state: Venezia
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore- dona Calabria di Negrar
state: Verona
city: Bologna
country: Italy
facility: Ospedale Bellaria
city: Brescia
country: Italy
facility: Azienda Ospedaliera "Spedali civili" di Brescia
city: Cuneo
country: Italy
facility: Ospedale Santa Croce e Carlè
city: Firenze
country: Italy
facility: Azienda Ospedaliera universitaria Careggi
city: Genova
country: Italy
facility: IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro
city: Mantova
country: Italy
facility: Ospedale Carlo Poma
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: Ospedale Niguarda Ca' Granda
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS - Fondazione Pascale
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Roma
country: Italy
facility: Policlinico Universitario Gemelli di Roma
city: Rovigo
country: Italy
facility: Ospedale Santa Maria della Misericordia
city: Torino
country: Italy
facility: A.O. Città della Salute e della Scienza - Ospedale Dermatologico S. Lazzaro
city: Trento
country: Italy
facility: Ospedale di Trento - Presidio Ospedaliero Santa Chiara
city: Treviso
country: Italy
facility: Azienda ULSS 9 Presidio Ospedaliero di Treviso
city: Venezia Mestre
country: Italy
facility: Azienda U.L.S.S. 12 Veneziana
Study officials:
affiliation: Fondazione IRCCS - Istituto Nazionale Tumori - Milano (Italy)
name: Lisa Licitra, MD
role: PRINCIPAL_INVESTIGATOR
References: