Clinical trial NCT01336530: Tepilta® Versus Oxetacaine, Antacids and Placebo
Official title: Clinical Trial to Assess the Efficacy of Fixed Combination Product Tepilta® in the Treatment of Radiation-induced Oesophagitis Compared to Its Active Ingredients Oxetacaine and Antacids, and to Placebo
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Radiation-induced Oesophagitis
Keywords: Oesophageal pain
Radiotherapy
Combined radio-chemotherapy
Oesophageal symptoms
Lead sponsor: Viatris Inc.
Sponsor class: INDUSTRY
Collaborators: name: Trium Analysis Online GmbH
name: ICON plc
name: Clinipace Worldwide
First posted: 2011-04-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomised, double-blind, placebo-controlled, therapeutic confirmatory multicentre trial with 4 parallel treatment groups. The design is adaptive group-sequential with two interim analyses, possible sample size re-estimation after the first or second interim analysis and drop-the-loser approach. The study design was primarily chosen to show superior efficacy of Tepilta® compared to the single components and to placebo. Evaluation of safety is a secondary objective.

Detailed description: Tepilta® Suspension is indicated for treatment of pain in the upper digestive system induced by radiation therapy, in particular for radiation-induced oesophagitis.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 18 years.
2. Score = 0 on NRS for oesophageal pain.
3. Radiotherapy (RT) or combined radio-chemotherapy (RCT) of a solid tumour in head/neck/thorax region. A minimum length of 5 cm of the oesophagus must be included in high-dose radiation field.
4. Duration of RT 5 to 8 weeks.
5. Single radiation dosage of fractionated RT 1.8 to 2.0 Gy/day, of intensity-modulated RT (IMRT) 1.5 to 2.3 Gy/day, each for 5 days a week (single frequency deviations are allowed presuming that intended duration of RT remains 5 to 8 weeks).
6. First radiation in the intended radiation area.
7. Written informed consent.

   Randomisation criteria:
8. Appearance of oesophageal pain as follows: Score ≥ 2 on Numeric Rating Scale (NRS) for pain during main daily meals is reached at least once.
9. At least 20 Gy of the dose of radiation therapy in oesophageal area remaining.
10. Oesophageal symptoms of grade ≤ 2a according to the adapted Common Terminology Criteria for Adverse Events CTCAE.

Exclusion Criteria:

1. History of allergic reaction to the study medication or its excipients (i.e. aluminium or magnesium hydroxide, oxetacaine, any other ingredient of study medication).
2. Pregnancy, breast-feeding or planned pregnancy during the study.
3. Known hypermagnesaemia.
4. Known hypophosphataemia.
5. Clinically significant obstipation, as judged by the investigator.
6. Acute appendicitis.
7. Total intended radiation dose at lips and the anterior oral cavity \> 60% of total intended radiation dose at the swallowing process (pharynx, oesophagus).
8. Hyper-fractionated RT.
9. Intended naso-gastral tubes.
10. Primary tumour of the cranial base, brain, oral cavity, lips, naso-pharynx, para-nasal sinuses.
11. Known bone metastases.
12. Reflux oesophagitis 3 months prior to the study.
13. Continuous systemic pain treatment at the beginning of RT. Systemic pain medication for oesophagitis prior to randomisation must not be taken.
14. Concomitant treatment with tetracyclines, cinolone derivatives (ciprofloxacin, ofloxacin, enoxacin, norfloxacin), cheno-desoxycholic acid, sodium fluoride, local anaesthetics (other than those used as study medication).
15. Patients relying on levothyroxine after resection of thyroid carcinoma being hypothyroid and patients relying on levothyroxine due to other reasons not being euthyroid.
16. Artificial nutrition at the beginning of radiation.
17. Drug (licit and illicit) or alcohol abuse which would interfere with the patient's proper completion of the study.
18. Exposure to an investigational product within the last 4 weeks, simultaneous exposure to another investigational product.
19. Lack of ability or willingness to give informed consent.
20. Anticipated non-availability for study visits / procedures.
21. Lack of ability or willingness to keep patient's diary.
22. Lack of willingness to have personal study related data collected, archived or transmitted according to the protocol.
23. Vulnerable subjects.

Primary outcomes:
measure: Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO).
timeFrame: up to 11 weeks
Secondary outcomes:
measure: ASPO: WHO analgesic pain ladder
timeFrame: up to 11 weeks
measure: Pain intensity recorded on NRS with scores 0-10
timeFrame: up to 11 weeks
measure: Swallowing disorder recorded on NRS with scores 0-10
timeFrame: up to 11 weeks
measure: Adapted CTCAE grade
timeFrame: up to 11 weeks
measure: Incidence of artificial nutrition due to radiation-induced oesophagitis
timeFrame: up to 11 weeks
measure: Incidence of interruptions of radiation therapy due to radiation-induced oesophagitis
timeFrame: up to 11 weeks
measure: Duration of pain medication intake after the end of Radiation Therapy
timeFrame: up to 11 weeks
measure: Loss of body weight
timeFrame: up to 11 weeks
Other outcomes:
Locations:
city: Feldkirch
country: Austria
facility: Landeskrankenhaus Feldkirch
city: Innsbruck
country: Austria
facility: Universitätsklinik für Strahlentherapie-Radioonkologie
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Altötting
country: Germany
facility: RADIO LOG Strahlentherapie Altötting
city: Bad Homburg
country: Germany
facility: please contact Dr. Ingrid Schwienhorst/MEDA for details
city: Berlin
country: Germany
facility: VIVANTES Klinikum Neukölln
city: Berlin
country: Germany
facility: Strahlenheilkunde Westend
city: Bielefeld
country: Germany
facility: Franziskus Hospital
city: Bochum
country: Germany
facility: Klinik für Hämatologie, Onkologie & Palliativmedizin
city: Bonn
country: Germany
facility: Strahlentherapie Bonn-Rhein-Sieg
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig GmbH
city: Coesfeld
country: Germany
facility: Strahlentherapie Coesfeld
city: Dortmund
country: Germany
facility: Knappschaftskrankenhaus Dortmund
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nordwest GmbH
city: Freising
country: Germany
facility: Strahlentherapie - Freising
city: Gummersbach
country: Germany
facility: Kreiskrankenhaus Gummersbach
city: Halle (Saale)
country: Germany
facility: Universitätsklinikum Halle (Saale)
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Herne
country: Germany
facility: Kath. Krankenhaus Marienhospital
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Marburg
country: Germany
facility: Klinik für Strahlentherapie und Radioonkologie
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
city: München
country: Germany
facility: Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum Schwabing
city: München
country: Germany
facility: Klinikum der Universität München
city: Osnabrück
country: Germany
facility: Paracelsus-Klinik Osnabrück
city: Ostfildern
country: Germany
facility: Paracelsus-Krankenhaus Ruit
city: Paderborn
country: Germany
facility: Brüderkrankenhaus St. Josef
city: Potsdam
country: Germany
facility: Klinikum Ernst von Bergmann
city: Recklinghausen
country: Germany
facility: Prosperhospital Recklinghausen
city: Rostock
country: Germany
facility: Universitätsklinikum Rostock AöR
city: Stuttgart
country: Germany
facility: Klinik für Radioonkologie und Strahlentherapie
Study officials:
affiliation: Hannover Medical School
name: Frank Bruns, Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: MEDA Pharma GmbH & Co. KG
name: Ursula Petzold, PhD
role: STUDY_CHAIR
References: