Tepilta® Versus Oxetacaine, Antacids and Placebo

Phase 3

Terminated

• Conditions: Radiation-induced Oesophagitis
• Interventions: Drug: oxetacaine; Drug: magnesium and aluminium hydroxide; Drug: oxetacaine, aluminium and magnesium hydroxide; Other: Vehicle

• Registration Number: NCT01336530
• Lead Sponsor: MEDA Pharma GmbH & Co. KG

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.

Study Timeline

• Study Start: 2011-04
• Study First Submitted: 2011-04-01
• Study First Submitted QC: 2011-04-14
• Study First Posted: 2011-04-18
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Status Verified: 2017-02
• Last Update Submitted: 2022-02-04
• Last Update Posted: 2022-02-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oxetacaine	oxetacaine	-
Antacids	magnesium and aluminium hydroxide	-
Tepilta®	oxetacaine, aluminium and magnesium hydroxide	-
Placebo	Vehicle	-

Primary Outcome Measures

Name	Time	Method
Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO).	up to 11 weeks

Secondary Outcome Measures

Name	Time	Method
Pain intensity recorded on NRS with scores 0-10	up to 11 weeks	NRS = Numeric Rating Scale
ASPO: WHO analgesic pain ladder	up to 11 weeks	ASPO = Additional systemic pain medication for oesophagitis
Incidence of artificial nutrition due to radiation-induced oesophagitis	up to 11 weeks
Incidence of interruptions of radiation therapy due to radiation-induced oesophagitis	up to 11 weeks
Loss of body weight	up to 11 weeks
Swallowing disorder recorded on NRS with scores 0-10	up to 11 weeks	NRS = Numeric Rating Scale
Duration of pain medication intake after the end of Radiation Therapy	up to 11 weeks
Adapted CTCAE grade	up to 11 weeks	CTCAE = Common Terminology Criteria for Adverse Events; Severity of oesophageal symptoms will be evaluated by the investigator according to an adapted CTCAE grading system. In contrast to the original CTCAE classification the adapted version foreseen to be used in this study distinguishes level 2a and 2b.; 2a = symptomatic; altered eating/swallowing; oral supplements indicated; requiring predominantly pureed or soft diet, 2b = symptomatic; altered eating/swallowing; oral supplements indicated; requiring predominantly liquid diet.

Trial Locations

Locations (32)

Landeskrankenhaus Feldkirch; 🇦🇹 Feldkirch, Austria

Strahlentherapie Coesfeld; 🇩🇪 Coesfeld, Germany

Universitätsklinik für Strahlentherapie-Radioonkologie; 🇦🇹 Innsbruck, Austria

Klinik für Hämatologie, Onkologie & Palliativmedizin; 🇩🇪 Bochum, Germany

Universitätsklinikum Aachen; 🇩🇪 Aachen, Germany

RADIO LOG Strahlentherapie Altötting; 🇩🇪 Altötting, Germany

please contact Dr. Ingrid Schwienhorst/MEDA for details; 🇩🇪 Bad Homburg, Germany

VIVANTES Klinikum Neukölln; 🇩🇪 Berlin, Germany

Strahlenheilkunde Westend; 🇩🇪 Berlin, Germany

Strahlentherapie Bonn-Rhein-Sieg; 🇩🇪 Bonn, Germany

Franziskus Hospital; 🇩🇪 Bielefeld, Germany

Städtisches Klinikum Braunschweig GmbH; 🇩🇪 Braunschweig, Germany

Klinikum Frankfurt (Oder) GmbH; 🇩🇪 Frankfurt (Oder), Germany

Knappschaftskrankenhaus Dortmund; 🇩🇪 Dortmund, Germany

Krankenhaus Nordwest GmbH; 🇩🇪 Frankfurt am Main, Germany

Strahlentherapie - Freising; 🇩🇪 Freising, Germany

Kreiskrankenhaus Gummersbach; 🇩🇪 Gummersbach, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Universitätsklinikum Halle (Saale); 🇩🇪 Halle (Saale), Germany

Kath. Krankenhaus Marienhospital; 🇩🇪 Herne, Germany

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Germany

Kliniken Maria Hilf GmbH; 🇩🇪 Mönchengladbach, Germany

Klinikum der Universität München; 🇩🇪 München, Germany

Klinik für Strahlentherapie und Radioonkologie; 🇩🇪 Marburg, Germany

Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum Schwabing; 🇩🇪 München, Germany

Paracelsus-Klinik Osnabrück; 🇩🇪 Osnabrück, Germany

Paracelsus-Krankenhaus Ruit; 🇩🇪 Ostfildern, Germany

Klinikum Ernst von Bergmann; 🇩🇪 Potsdam, Germany

Prosperhospital Recklinghausen; 🇩🇪 Recklinghausen, Germany

Brüderkrankenhaus St. Josef; 🇩🇪 Paderborn, Germany

Universitätsklinikum Rostock AöR; 🇩🇪 Rostock, Germany

Klinik für Radioonkologie und Strahlentherapie; 🇩🇪 Stuttgart, Germany