Clinical study comparing the product Tepilta® with its two active ingredients and with placebo in the treatment of radiation-induced oesophagitis

Phase 1

Conditions: Radiation-induced oesophagitis
MedDRA version: 19.1Level: PTClassification code 10048899Term: Radiation oesophagitisSystem Organ Class: 10022117 - Injury, poisoning and procedural complications
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2009-014441-93-DE

Lead Sponsor: MEDA Pharma GmbH & Co. KG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 810

Inclusion Criteria

Screening 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 radiotherapy 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 (not tumour-induced) 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 for oesophagitis.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 405
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 405

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. Women of child bearing potential not using highly effective methods of birth control defined as those which result in a low failure rate (i.e. <1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, tubal ligation or vasectomised partner.
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 organs (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 (from medical history).
13. Continuous systemic pain treatment at the beginning of RT. Systemic pain medication for oesophagitis prior to randomisation must not be taken. Temporary intake of systemic non-oesophageal pain medication prior to randomisation is allowed as judged by the investigator. However, 3 days before randomisation systemic non-oesophageal pain medication must not be taken.
14. Concomitant treatment with tetracyclines, chinolone derivatives (ciprofloxacine, ofloxacine, enoxacine, norfloxacine), 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 levothyroxin due to other reasons not being euthyroid.
16. Artificial nutrition at the beginning of radiation (artificial nutrition defined as infusions of fats, trace minerals, protein, vitamins, and high-dose carbohydrates by indwelling venous cannulas, PEG tubes, CVCs (central venous catheters) or ports.
Artificial nutrition is not meant as infusions of fluid, electrolytes or glucose.).
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 (such as persons kept in detention).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objective:<br>• To prove the combination effect of oxetacaine and antacids, i.e. to demonstrate<br>superior efficacy of Tepilta® versus oxetacaine, antacids, and placebo.<br>;Secondary Objective: Secondary objectives:<br>• To further evaluate safety of Tepilta®.;Primary end point(s): Efficacy:<br>ASPO: Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO).<br>;Timepoint(s) of evaluation of this end point: First interim analysis around 2013, second interim analysis around 2014/2015, final analysis around 2016

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy:<br>ASPO: WHO analgesic pain ladder;<br>Pain intensity (oesophageal pain during main meals of the day) recorded on NRS with scores 0 to 10;<br>Swallowing disorder recorded on NRS with scores 0 to 10;<br>Adapted CTCAE grade for oesophagitis;<br>Incidence of artificial nutrition due to radiation-induced oesophagitis;<br>Incidence of interruptions of radiation therapy due to radiation-induced oesophagitis;<br>Duration of pain medication intake after the end of RT (in days);<br>Loss of body weight;<br>Global assessment of efficacy by investigator.<br>Safety:<br>Adverse events.<br>Global assessment of safety by investigator.;Timepoint(s) of evaluation of this end point: First interim analysis around 2013, second interim analysis around 2014/2015, final analysis around 2018

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