Tepilta® Versus Oxetacaine, Antacids and Placebo
Primary Purpose
Radiation-induced Oesophagitis
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
oxetacaine, aluminium and magnesium hydroxide
oxetacaine
magnesium and aluminium hydroxide
Vehicle
Sponsored by
About this trial
This is an interventional treatment trial for Radiation-induced Oesophagitis focused on measuring Oesophageal pain, Radiotherapy, Combined radio-chemotherapy, Oesophageal symptoms
Eligibility Criteria
Inclusion Criteria:
- Male or female ≥ 18 years.
- Score = 0 on NRS for oesophageal pain.
- 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.
- Duration of RT 5 to 8 weeks.
- 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).
- First radiation in the intended radiation area.
Written informed consent.
Randomisation criteria:
- Appearance of oesophageal pain as follows: Score ≥ 2 on Numeric Rating Scale (NRS) for pain during main daily meals is reached at least once.
- At least 20 Gy of the dose of radiation therapy in oesophageal area remaining.
- Oesophageal symptoms of grade ≤ 2a according to the adapted Common Terminology Criteria for Adverse Events CTCAE.
Exclusion Criteria:
- History of allergic reaction to the study medication or its excipients (i.e. aluminium or magnesium hydroxide, oxetacaine, any other ingredient of study medication).
- Pregnancy, breast-feeding or planned pregnancy during the study.
- Known hypermagnesaemia.
- Known hypophosphataemia.
- Clinically significant obstipation, as judged by the investigator.
- Acute appendicitis.
- Total intended radiation dose at lips and the anterior oral cavity > 60% of total intended radiation dose at the swallowing process (pharynx, oesophagus).
- Hyper-fractionated RT.
- Intended naso-gastral tubes.
- Primary tumour of the cranial base, brain, oral cavity, lips, naso-pharynx, para-nasal sinuses.
- Known bone metastases.
- Reflux oesophagitis 3 months prior to the study.
- Continuous systemic pain treatment at the beginning of RT. Systemic pain medication for oesophagitis prior to randomisation must not be taken.
- Concomitant treatment with tetracyclines, cinolone derivatives (ciprofloxacin, ofloxacin, enoxacin, norfloxacin), cheno-desoxycholic acid, sodium fluoride, local anaesthetics (other than those used as study medication).
- Patients relying on levothyroxine after resection of thyroid carcinoma being hypothyroid and patients relying on levothyroxine due to other reasons not being euthyroid.
- Artificial nutrition at the beginning of radiation.
- Drug (licit and illicit) or alcohol abuse which would interfere with the patient's proper completion of the study.
- Exposure to an investigational product within the last 4 weeks, simultaneous exposure to another investigational product.
- Lack of ability or willingness to give informed consent.
- Anticipated non-availability for study visits / procedures.
- Lack of ability or willingness to keep patient's diary.
- Lack of willingness to have personal study related data collected, archived or transmitted according to the protocol.
- Vulnerable subjects.
Sites / Locations
- Landeskrankenhaus Feldkirch
- Universitätsklinik für Strahlentherapie-Radioonkologie
- Universitätsklinikum Aachen
- RADIO LOG Strahlentherapie Altötting
- please contact Dr. Ingrid Schwienhorst/MEDA for details
- VIVANTES Klinikum Neukölln
- Strahlenheilkunde Westend
- Franziskus Hospital
- Klinik für Hämatologie, Onkologie & Palliativmedizin
- Strahlentherapie Bonn-Rhein-Sieg
- Städtisches Klinikum Braunschweig GmbH
- Strahlentherapie Coesfeld
- Knappschaftskrankenhaus Dortmund
- Klinikum Frankfurt (Oder) GmbH
- Krankenhaus Nordwest GmbH
- Strahlentherapie - Freising
- Kreiskrankenhaus Gummersbach
- Universitätsklinikum Halle (Saale)
- Medizinische Hochschule Hannover
- Kath. Krankenhaus Marienhospital
- Universitätsklinikum Leipzig
- Klinik für Strahlentherapie und Radioonkologie
- Kliniken Maria Hilf GmbH
- Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum Schwabing
- Klinikum der Universität München
- Paracelsus-Klinik Osnabrück
- Paracelsus-Krankenhaus Ruit
- Brüderkrankenhaus St. Josef
- Klinikum Ernst von Bergmann
- Prosperhospital Recklinghausen
- Universitätsklinikum Rostock AöR
- Klinik für Radioonkologie und Strahlentherapie
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Tepilta®
Oxetacaine
Antacids
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO).
Secondary Outcome Measures
ASPO: WHO analgesic pain ladder
ASPO = Additional systemic pain medication for oesophagitis
Pain intensity recorded on NRS with scores 0-10
NRS = Numeric Rating Scale
Swallowing disorder recorded on NRS with scores 0-10
NRS = Numeric Rating Scale
Adapted CTCAE grade
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.
Incidence of artificial nutrition due to radiation-induced oesophagitis
Incidence of interruptions of radiation therapy due to radiation-induced oesophagitis
Duration of pain medication intake after the end of Radiation Therapy
Loss of body weight
Full Information
NCT ID
NCT01336530
First Posted
April 1, 2011
Last Updated
February 4, 2022
Sponsor
MEDA Pharma GmbH & Co. KG
Collaborators
Trium Analysis Online GmbH, ICON plc, Clinipace Worldwide
1. Study Identification
Unique Protocol Identification Number
NCT01336530
Brief Title
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
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Why Stopped
The study stopped prematurely due to and administrative reasons, not based on grounds of safety.
Study Start Date
April 2011 (Actual)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MEDA Pharma GmbH & Co. KG
Collaborators
Trium Analysis Online GmbH, ICON plc, Clinipace Worldwide
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Radiation-induced Oesophagitis
Keywords
Oesophageal pain, Radiotherapy, Combined radio-chemotherapy, Oesophageal symptoms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tepilta®
Arm Type
Experimental
Arm Title
Oxetacaine
Arm Type
Active Comparator
Arm Title
Antacids
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
oxetacaine, aluminium and magnesium hydroxide
Other Intervention Name(s)
Tepilta®
Intervention Description
20mg/10ml oxetacaine, 196mg/10ml magnesium hydroxide, 582mg/10ml aluminium hydroxide. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.
Intervention Type
Drug
Intervention Name(s)
oxetacaine
Intervention Description
20mg/10ml oxetacaine. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.
Intervention Type
Drug
Intervention Name(s)
magnesium and aluminium hydroxide
Other Intervention Name(s)
Antacids
Intervention Description
196mg/10ml magnesium hydroxide, 582mg/10ml aluminium hydroxide. Suspension for oral intake 3-6 times per day for a maximum of 11 weeks.
Intervention Type
Other
Intervention Name(s)
Vehicle
Intervention Description
Placebo suspension for oral intake 3-6 times per day for a maximum of 11 weeks.
Primary Outcome Measure Information:
Title
Time from randomisation to requirement of additional systemic pain medication for oesophagitis (ASPO).
Time Frame
up to 11 weeks
Secondary Outcome Measure Information:
Title
ASPO: WHO analgesic pain ladder
Description
ASPO = Additional systemic pain medication for oesophagitis
Time Frame
up to 11 weeks
Title
Pain intensity recorded on NRS with scores 0-10
Description
NRS = Numeric Rating Scale
Time Frame
up to 11 weeks
Title
Swallowing disorder recorded on NRS with scores 0-10
Description
NRS = Numeric Rating Scale
Time Frame
up to 11 weeks
Title
Adapted CTCAE grade
Description
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.
Time Frame
up to 11 weeks
Title
Incidence of artificial nutrition due to radiation-induced oesophagitis
Time Frame
up to 11 weeks
Title
Incidence of interruptions of radiation therapy due to radiation-induced oesophagitis
Time Frame
up to 11 weeks
Title
Duration of pain medication intake after the end of Radiation Therapy
Time Frame
up to 11 weeks
Title
Loss of body weight
Time Frame
up to 11 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female ≥ 18 years.
Score = 0 on NRS for oesophageal pain.
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.
Duration of RT 5 to 8 weeks.
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).
First radiation in the intended radiation area.
Written informed consent.
Randomisation criteria:
Appearance of oesophageal pain as follows: Score ≥ 2 on Numeric Rating Scale (NRS) for pain during main daily meals is reached at least once.
At least 20 Gy of the dose of radiation therapy in oesophageal area remaining.
Oesophageal symptoms of grade ≤ 2a according to the adapted Common Terminology Criteria for Adverse Events CTCAE.
Exclusion Criteria:
History of allergic reaction to the study medication or its excipients (i.e. aluminium or magnesium hydroxide, oxetacaine, any other ingredient of study medication).
Pregnancy, breast-feeding or planned pregnancy during the study.
Known hypermagnesaemia.
Known hypophosphataemia.
Clinically significant obstipation, as judged by the investigator.
Acute appendicitis.
Total intended radiation dose at lips and the anterior oral cavity > 60% of total intended radiation dose at the swallowing process (pharynx, oesophagus).
Hyper-fractionated RT.
Intended naso-gastral tubes.
Primary tumour of the cranial base, brain, oral cavity, lips, naso-pharynx, para-nasal sinuses.
Known bone metastases.
Reflux oesophagitis 3 months prior to the study.
Continuous systemic pain treatment at the beginning of RT. Systemic pain medication for oesophagitis prior to randomisation must not be taken.
Concomitant treatment with tetracyclines, cinolone derivatives (ciprofloxacin, ofloxacin, enoxacin, norfloxacin), cheno-desoxycholic acid, sodium fluoride, local anaesthetics (other than those used as study medication).
Patients relying on levothyroxine after resection of thyroid carcinoma being hypothyroid and patients relying on levothyroxine due to other reasons not being euthyroid.
Artificial nutrition at the beginning of radiation.
Drug (licit and illicit) or alcohol abuse which would interfere with the patient's proper completion of the study.
Exposure to an investigational product within the last 4 weeks, simultaneous exposure to another investigational product.
Lack of ability or willingness to give informed consent.
Anticipated non-availability for study visits / procedures.
Lack of ability or willingness to keep patient's diary.
Lack of willingness to have personal study related data collected, archived or transmitted according to the protocol.
Vulnerable subjects.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Bruns, Dr. med.
Organizational Affiliation
Hannover Medical School
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ursula Petzold, PhD
Organizational Affiliation
MEDA Pharma GmbH & Co. KG
Official's Role
Study Chair
Facility Information:
Facility Name
Landeskrankenhaus Feldkirch
City
Feldkirch
ZIP/Postal Code
6807
Country
Austria
Facility Name
Universitätsklinik für Strahlentherapie-Radioonkologie
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
Universitätsklinikum Aachen
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
RADIO LOG Strahlentherapie Altötting
City
Altötting
ZIP/Postal Code
84503
Country
Germany
Facility Name
please contact Dr. Ingrid Schwienhorst/MEDA for details
City
Bad Homburg
Country
Germany
Facility Name
VIVANTES Klinikum Neukölln
City
Berlin
ZIP/Postal Code
12351
Country
Germany
Facility Name
Strahlenheilkunde Westend
City
Berlin
ZIP/Postal Code
14050
Country
Germany
Facility Name
Franziskus Hospital
City
Bielefeld
ZIP/Postal Code
33615
Country
Germany
Facility Name
Klinik für Hämatologie, Onkologie & Palliativmedizin
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Strahlentherapie Bonn-Rhein-Sieg
City
Bonn
ZIP/Postal Code
53177
Country
Germany
Facility Name
Städtisches Klinikum Braunschweig GmbH
City
Braunschweig
ZIP/Postal Code
38114
Country
Germany
Facility Name
Strahlentherapie Coesfeld
City
Coesfeld
ZIP/Postal Code
48653
Country
Germany
Facility Name
Knappschaftskrankenhaus Dortmund
City
Dortmund
ZIP/Postal Code
44309
Country
Germany
Facility Name
Klinikum Frankfurt (Oder) GmbH
City
Frankfurt (Oder)
ZIP/Postal Code
15236
Country
Germany
Facility Name
Krankenhaus Nordwest GmbH
City
Frankfurt am Main
ZIP/Postal Code
60488
Country
Germany
Facility Name
Strahlentherapie - Freising
City
Freising
ZIP/Postal Code
85354
Country
Germany
Facility Name
Kreiskrankenhaus Gummersbach
City
Gummersbach
ZIP/Postal Code
51643
Country
Germany
Facility Name
Universitätsklinikum Halle (Saale)
City
Halle (Saale)
ZIP/Postal Code
06110
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Kath. Krankenhaus Marienhospital
City
Herne
ZIP/Postal Code
44625
Country
Germany
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Klinik für Strahlentherapie und Radioonkologie
City
Marburg
ZIP/Postal Code
35033
Country
Germany
Facility Name
Kliniken Maria Hilf GmbH
City
Mönchengladbach
ZIP/Postal Code
41063
Country
Germany
Facility Name
Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum Schwabing
City
München
ZIP/Postal Code
80804
Country
Germany
Facility Name
Klinikum der Universität München
City
München
ZIP/Postal Code
81377
Country
Germany
Facility Name
Paracelsus-Klinik Osnabrück
City
Osnabrück
ZIP/Postal Code
49076
Country
Germany
Facility Name
Paracelsus-Krankenhaus Ruit
City
Ostfildern
ZIP/Postal Code
73760
Country
Germany
Facility Name
Brüderkrankenhaus St. Josef
City
Paderborn
ZIP/Postal Code
33098
Country
Germany
Facility Name
Klinikum Ernst von Bergmann
City
Potsdam
ZIP/Postal Code
14467
Country
Germany
Facility Name
Prosperhospital Recklinghausen
City
Recklinghausen
ZIP/Postal Code
45659
Country
Germany
Facility Name
Universitätsklinikum Rostock AöR
City
Rostock
ZIP/Postal Code
18059
Country
Germany
Facility Name
Klinik für Radioonkologie und Strahlentherapie
City
Stuttgart
ZIP/Postal Code
70174
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Tepilta® Versus Oxetacaine, Antacids and Placebo
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