Oral MucositisPhase 1/2MUCOMELNCT02630004
Melatonin Oral Gel for Oral Mucositis in Patients With Head and Neck Cancer Undergoing Chemoradiation
A Phase 1/2 study testing Melatonin oral gel 3% in people with Oral Mucositis, run by Spherium Biomed at 11 sites in Spain.
Trial summary
The main purpose of this study is to assess the efficacy of melatonin oral gel compared to placebo in the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing concurrent chemoradiation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oral Mucositis
- What is being tested?
- Melatonin oral gel 3%
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 11 sitesSpain
- Study dates
- Nov 2015to 22 Dec 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients 18 years or over.
- Patients who gave written informed consent.
- Life expectancy ≥ 3 months.
- Subjects willing to comply with treatment and follow-up.
- Histologically confirmed diagnosis of non-metastatic TNM-2010 stage III-IV squamous cell carcinoma of the following sites:
- oral cavity
Show all 25Show fewer
- oropharynx
- or any Head and Neck site with lymph nodes at cervical level II.
- Or histologically confirmed carcinoma of the nasopharynx (differentiated squamous cell carcinoma or NonKeratinizing carcinoma or undifferentiated carcinoma) found eligible for chemoradiation with or without neoadjuvant chemotherapy.
- Patients who have a treatment plan based on systemic treatment (cisplatin or cetuximab) concurrent with radiation with curative intent. Patients may have received up to 3 cycles of neoadjuvant chemotherapy if local adverse events related to this treatment are fully resolved before study entry. Patients with a plan of postoperative chemoradiation may be included only if the primary tumour is located in the oral cavity.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
- Adequate baseline organ function (hematologic, liver, renal, nutritional and metabolic):
- Haematology:
- Absolute neutrophil count (ANC) ≥1.5 x 109/L
- Haemoglobin ≥ 10 g/dL
- Platelets ≥ 100,000 x 109/L
- Hepatic:
- Total bilirubin ≤ 2 X (Upper limit normal) ULN
- Alanine amino transferase (ALT) and Asparatate aminotransferase (AST) ≤5 x ULN
- Renal:
- For patients who will receive cisplatin: Serum creatinine ≤ ULN or, if > ULN calculated creatinine clearance (ClCR) ≥ 60 mL/min.
- For patients who will receive cetuximab: Serum creatinine <2.0 mg/dl.
- Nutritional and metabolic:
- Albumin > 3.0 mg/dl
- Magnesium > lower limit normal (LLN) for patients who will receive cetuximab
Who cannot join
- Patients with blistering disease.
- Patients who require feeding with either nasogastric tube, gastrostomy or jejunostomy at study entry
- Patients whose radiotherapy treatment planned dose is lower than 66 Gy
- Patients being receiving another investigational agent because of participation in another therapeutic trial
- Patients treated with fluvoxamine, estrogens, cimetidine, 5- and 8 methoxypsoralen and/or carbamazepine
- Active viral, bacterial or fungal infections of the mouth in the last 14 days (i.e. stomatitis related to herpes virus or candida)
Show all 15Show fewer
- Pregnancy or lactation
- Known allergy to melatonin
- Prior radiotherapy of the head and neck
- Patients with a treatment plan consisting of chemoradiation followed by further chemotherapy
- Patients with a diagnostics of a synchronic neoplasia except for non-melanoma skin cancer curable with local treatment or in situ cervix carcinoma
- Any investigational agent within 30 days prior to inclusion
- Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, i.e. use contraception double barrier (e.g. diaphragm plus condoms) or abstinence during the course of the study and for 2 months after the last administration of the study drug for women and 1 month for men
- Psychological, geographical, familial or sociological conditions that potentially prevent compliance with the study protocol and follow-up schedule according to investigator criteria. These conditions should be discussed with the patient before inclusion in the trial.
- Any other medical condition that would make the patient inappropiate for study participation according to the Investigator's judgement.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Spain11 sites
Institut Català d'Oncologia ICO Badalona
Badalona, Barcelona, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, 08026
Hospital Universitari de la Vall d'Hebron
Barcelona, 08035
Institut Català d'Oncologia Girona
Girona, 17007
Institut Català d'Oncologia L'Hospitalet
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital San Carlos, Madrid
Madrid, 28040
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Hospital Universitario Marqués de Valdecilla
Santander, 39008
Hospital Clínico Universitario de Santiago
Santiago de Compostela, La Coruña, 15706
Hospital Miguel Servet
Zaragoza, 50009
About this study
Official title: Phase IB-II Clinical Trial of Melatonin Oral Gel for the Prevention and Treatment of Oral Mucositis in Patients With Head and Neck Cancer Undergoing Chemoradiation.
The main purpose of this study is to assess the efficacy of melatonin oral gel compared to placebo in the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing concurrent chemoradiation.
Other objectives are to assess the Quality of Life (QoL), to evaluate the safety and tolerability and to assess the pharmacokinetic profile of melatonin oral gel administration, in all cases compared to placebo in patients with head and neck cancer and oral mucositis secondary to concurrent chemoradiation.
Read the detailed description
The study is designed as a prospective, randomized, double blind and placebo-controlled study.
Eligible patients with head and neck cancer undergoing chemoradiation will be randomized assigned at one-to-one ratio to receive
- Group A: melatonin oral gel 3%
- Group B: placebo
All patients will receive standard symptomatic treatment for oral mucositis along the study according to routine clinical practice of the hospital.
A full PK and safety assessment will be carried out in the first 24 patients included in the study (PK subgroup).
All patients will take melatonin oral gel 3% or placebo oral gel from two to three days before start of systemic treatment until one to four weeks after completion of radiotherapy. In the case of concurrent chemotherapy with cisplatin, patients will remain on study from the first day of chemoradiotherapy during 19 weeks (seven on chemoradiotherapy treatment, a maximum of four weeks after completion of radiotherapy and eight more weeks on observation). In the case of patients receiving cetuximab, since the first infusion of cetuximab will be administered one week before the first day of radiation, the patients will remain on study during 20 weeks (eight weeks on chemoradiotherapy, a maximum of four weeks after completion of radiotherapy and eight more weeks on observation). Investigators should take into account that the minimum duration of the melatonin oral gel 3% treatment would be 8 weeks for patients treated with cisplatin and 9 weeks for patients treated with cetuximab.
Patients with oral mucositis improved to grade 1 (based on RTOG) until one to four weeks after the end of chemoradiation may stop melatonin oral gel 3% or placebo treatments. Patients with grade ≥ 2 oral mucositis at this time-point (four weeks after the end of chemoradiation) will stop treatment per protocol (melatonin or placebo) and will continue with standard treatments and under observation until the last safety visit.
- Conditions
- Oral Mucositis
- Being tested
- Melatonin oral gel 3%, Placebo oral gel
- Keywords
- Mucositis, Head and Neck cancer, Chemoradiation
- Medical subject headings
- Stomatitis, Mucositis, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Melatonin oral gel 3%Drug
Placebo oral gelDrug
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Experimental | Melatonin oral gel 3% Receives: Drug: Melatonin oral gel 3% |
| Placebo | Placebo comparator | Placebo oral gel Receives: Drug: Placebo oral gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number (percentage) of patients who develop severe oral mucositis (grade 3-4 according to the RTOG scale)
Measured: up to 19-20 weeks
Secondary outcomes (17)
Number (percentage) of patients who develop severe oral mucositis (grade 3-4 according to NCI-CTCAE)
Measured: up to 19-20 weeks
Number of days with mucositis of any grade according to the RTOG scale
Measured: up to 19-20 weeks
Number of days with grade 3-4 mucositis according to the RTOG scale
Measured: up to 19-20 weeks
Time to onset of grade 3-4 mucositis according to the RTOG scale from starting systemic antineoplastic treatment
Measured: up to 19-20 weeks
Change from baseline in EORTC QLQ-C30 and EORTC QLQ-H&N35 scores at 4w after RT start
Measured: up to 4-5 weeks
Change from baseline in EORTC QLQ-C30 and EORTC QLQ-H&N35 scores at one week after completion of RT
Measured: up to 8-9 weeks
Change from baseline in EORTC QLQ-C30 and EORTC QLQ-H&N35 scores at 3 months after completion of RT or before surgery - if it is required post-chemoradiation due persistent or recurrent disease
Measured: up to 19-20 weeks
Change from baseline in ECOG-Performance status score at different time points along the study
Measured: up to 19-20 weeks
Number (percentage) of patients with grade 1-4 NCI-CTCAE adverse events related to IMP (melatonin oral gel 3%)
Measured: up to 19-20 weeks
Number (percentage) of patients who develop cisplatin or cetuximab-associated grade 1-4 adverse events according to the NCI-CTCAE scale
Measured: up to 19-20 weeks
Number (percentage) of patients who develop radiation-associated adverse events different from oral mucositis according to the RTOG scale
Measured: up to 19-20 weeks
Pharmacokinetics evaluation [Cmax]
Measured: up to 11-12 weeks
Pharmacokinetics evaluation [Tmax]
Measured: up to 11-12 weeks
Pharmacokinetics evaluation [AUC]
Measured: up to 11-12 weeks
Pharmacokinetics evaluation [T1/2]
Measured: up to 11-12 weeks
Pharmacokinetics evaluation [Vd]
Measured: up to 11-12 weeks
Pharmacokinetics evaluation [Clearance]
Measured: up to 11-12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2015 (estimated)
- Study startNov 2015
- Primary completionDec 2017
- Study completion22 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oral MucositisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spherium Biomed
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Institut Català d'Oncologia L'Hospitalet, Hospital Universitari de la Vall de Hebron, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut Català d'Oncologia ICO Girona, Institut Català d'Oncologia ICO Badalona, Hospital Miguel Servet, Hospital Universitario La Paz, Hospital Universitario Marqués de Valdecilla, Hospital Universitario Virgen de la Victoria, Hospital San Carlos, Madrid, Hospital Clinico Universitario de Santiago
- Responsible party
- Sponsor
- Investigators
- Alicia Lozano, MD, Principal investigator, Institut Català d'Oncologia L'Hospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02630004
- Sponsor's protocol ID
- JAN13004-30
- Acronym
- MUCOMEL
- Status last verified
- Feb 2018
- First submitted
- 3 Dec 2015
- Last updated
- 1 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IB-II Clinical Trial of Melatonin Oral Gel for the Prevention and Treatment of Oral Mucositis in Patients With Head and Neck Cancer Undergoing Chemoradiation.
- ClinicalTrials.gov ID
- NCT02630004
- Acronym / sponsor ID
- MUCOMEL / JAN13004-30
- Conditions
- Oral Mucositis
- Keywords
- Mucositis, Head and Neck cancer, Chemoradiation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Spherium BiomedIndustry (pharma, biotech, devices)
- Collaborators
- Institut Català d'Oncologia L'Hospitalet, Hospital Universitari de la Vall de Hebron, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut Català d'Oncologia ICO Girona, Institut Català d'Oncologia ICO Badalona, Hospital Miguel Servet, Hospital Universitario La Paz, Hospital Universitario Marqués de Valdecilla, Hospital Universitario Virgen de la Victoria, Hospital San Carlos, Madrid, Hospital Clinico Universitario de Santiago
- Study start
- Nov 2015
- Primary completion
- Dec 2017 (actual)
- Study completion
- 22 Dec 2017 (actual)
- First posted
- 15 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to assess the efficacy of melatonin oral gel compared to placebo in the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing concurrent chemoradiation.
Other objectives are to assess the Quality of Life (QoL), to evaluate the safety and tolerability and to assess the pharmacokinetic profile of melatonin oral gel administration, in all cases compared to placebo in patients with head and neck cancer and oral mucositis secondary to concurrent chemoradiation.
Detailed description
The study is designed as a prospective, randomized, double blind and placebo-controlled study.
Eligible patients with head and neck cancer undergoing chemoradiation will be randomized assigned at one-to-one ratio to receive
- Group A: melatonin oral gel 3%
- Group B: placebo
All patients will receive standard symptomatic treatment for oral mucositis along the study according to routine clinical practice of the hospital.
A full PK and safety assessment will be carried out in the first 24 patients included in the study (PK subgroup).
All patients will take melatonin oral gel 3% or placebo oral gel from two to three days before start of systemic treatment until one to four weeks after completion of radiotherapy. In the case of concurrent chemotherapy with cisplatin, patients will remain on study from the first day of chemoradiotherapy during 19 weeks (seven on chemoradiotherapy treatment, a maximum of four weeks after completion of radiotherapy and eight more weeks on observation). In the case of patients receiving cetuximab, since the first infusion of cetuximab will be administered one week before the first day of radiation, the patients will remain on study during 20 weeks (eight weeks on chemoradiotherapy, a maximum of four weeks after completion of radiotherapy and eight more weeks on observation). Investigators should take into account that the minimum duration of the melatonin oral gel 3% treatment would be 8 weeks for patients treated with cisplatin and 9 weeks for patients treated with cetuximab.
Patients with oral mucositis improved to grade 1 (based on RTOG) until one to four weeks after the end of chemoradiation may stop melatonin oral gel 3% or placebo treatments. Patients with grade ≥ 2 oral mucositis at this time-point (four weeks after the end of chemoradiation) will stop treatment per protocol (melatonin or placebo) and will continue with standard treatments and under observation until the last safety visit.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Experimental | Drug: Melatonin oral gel 3%Melatonin oral gel 3% |
| Placebo | Placebo comparator | Drug: Placebo oral gelPlacebo oral gel |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Male and female patients 18 years or over.
- Patients who gave written informed consent.
- Life expectancy ≥ 3 months.
- Subjects willing to comply with treatment and follow-up.
- Histologically confirmed diagnosis of non-metastatic TNM-2010 stage III-IV squamous cell carcinoma of the following sites:
Key exclusion criteria (15 listed)
- Patients with blistering disease.
- Patients who require feeding with either nasogastric tube, gastrostomy or jejunostomy at study entry
- Patients whose radiotherapy treatment planned dose is lower than 66 Gy
- Patients being receiving another investigational agent because of participation in another therapeutic trial
- Patients treated with fluvoxamine, estrogens, cimetidine, 5- and 8 methoxypsoralen and/or carbamazepine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Melatonin oral gel 3% | Drug | Melatonin |
| Placebo oral gel | Drug | Placebo |
Primary outcome
Number (percentage) of patients who develop severe oral mucositis (grade 3-4 according to the RTOG scale)
Time frame: up to 19-20 weeks
17 secondary outcomes
Number (percentage) of patients who develop severe oral mucositis (grade 3-4 according to NCI-CTCAE)
Time frame: up to 19-20 weeks
Number of days with mucositis of any grade according to the RTOG scale
Time frame: up to 19-20 weeks
Number of days with grade 3-4 mucositis according to the RTOG scale
Time frame: up to 19-20 weeks
Time to onset of grade 3-4 mucositis according to the RTOG scale from starting systemic antineoplastic treatment
Time frame: up to 19-20 weeks
Change from baseline in EORTC QLQ-C30 and EORTC QLQ-H&N35 scores at 4w after RT start
Time frame: up to 4-5 weeks
Change from baseline in EORTC QLQ-C30 and EORTC QLQ-H&N35 scores at one week after completion of RT
Time frame: up to 8-9 weeks
Change from baseline in EORTC QLQ-C30 and EORTC QLQ-H&N35 scores at 3 months after completion of RT or before surgery - if it is required post-chemoradiation due persistent or recurrent disease
Time frame: up to 19-20 weeks
Change from baseline in ECOG-Performance status score at different time points along the study
Time frame: up to 19-20 weeks
Number (percentage) of patients with grade 1-4 NCI-CTCAE adverse events related to IMP (melatonin oral gel 3%)
Time frame: up to 19-20 weeks
Number (percentage) of patients who develop cisplatin or cetuximab-associated grade 1-4 adverse events according to the NCI-CTCAE scale
Time frame: up to 19-20 weeks
Number (percentage) of patients who develop radiation-associated adverse events different from oral mucositis according to the RTOG scale
Time frame: up to 19-20 weeks
Pharmacokinetics evaluation [Cmax]
Time frame: up to 11-12 weeks
Pharmacokinetics evaluation [Tmax]
Time frame: up to 11-12 weeks
Pharmacokinetics evaluation [AUC]
Time frame: up to 11-12 weeks
Pharmacokinetics evaluation [T1/2]
Time frame: up to 11-12 weeks
Pharmacokinetics evaluation [Vd]
Time frame: up to 11-12 weeks
Pharmacokinetics evaluation [Clearance]
Time frame: up to 11-12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2018.
- Individual participant dataSharing planned: Undecided
Related trials for Oral Mucositis
Not yet recruiting
Recurrent Aphthous Stomatitis Management in Children Using Diode Laser 980 Nanometer Versus Hyaluronic Acid Gel (RCT)
Apthous Ulcer
RecruitingPhase 2
Traditional Chinese Medicine Preparation Alleviates Radiotherapy-induced Oral Mucositis in Head and Neck Cancer Patients.
Radiotherapy-induced Oral Mucositis
RecruitingPhase 3
High-dose Prophylactic Gabapentin (HOPE) vs. Placebo to Prevent Opioid Use for Oral Mucositis Pain During Concurrent Chemoradiation for Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma, Stage I Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
RecruitingObservational study
Evaluation of 25(OH)D3 and LL-37 Levels in Periimplant Sulcus Fluid
Peri Implantitis, Peri Implant Mucositis
RecruitingPhase 2
Taurine for the Prevention and Treatment of Radiation-induced Oral Mucositis in Patients With Nasopharyngeal Carcinoma
Oral Mucositis (Ulcerative) Due to Radiation, Nasopharyngeal Carcinoma (NPC)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alicia Lozano, MD principal investigator
Institut Català d'Oncologia L'Hospitalet
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Melatonin oral gel 3% in people with Oral Mucositis, run by Spherium Biomed at 11 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number (percentage) of patients who develop severe oral mucositis (grade 3-4 according to the RTOG scale) (time frame: up to 19-20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2018.