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Melatonin Oral Gel for Oral Mucositis in Patients With Head and Neck Cancer Undergoing Chemoradiation (MUCOMEL)

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ClinicalTrials.gov Identifier: NCT02630004
Recruitment Status : Completed
First Posted : December 15, 2015
Last Update Posted : March 1, 2018
Sponsor:
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
Information provided by (Responsible Party):
Spherium Biomed

Brief 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.

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.


Condition or disease Intervention/treatment Phase
Oral Mucositis Drug: Melatonin oral gel 3% Drug: Placebo oral gel Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
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.
Study Start Date : November 2015
Actual Primary Completion Date : December 2017
Actual Study Completion Date : December 22, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Melatonin

Arm Intervention/treatment
Experimental: Melatonin
Melatonin oral gel 3%
Drug: Melatonin oral gel 3%
Placebo Comparator: Placebo
Placebo oral gel
Drug: Placebo oral gel



Primary Outcome Measures :
  1. Number (percentage) of patients who develop severe oral mucositis (grade 3-4 according to the RTOG scale) [ Time Frame: up to 19-20 weeks ]

Secondary Outcome Measures :
  1. Number (percentage) of patients who develop severe oral mucositis (grade 3-4 according to NCI-CTCAE) [ Time Frame: up to 19-20 weeks ]
  2. Number of days with mucositis of any grade according to the RTOG scale [ Time Frame: up to 19-20 weeks ]
  3. Number of days with grade 3-4 mucositis according to the RTOG scale [ Time Frame: up to 19-20 weeks ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. Change from baseline in ECOG-Performance status score at different time points along the study [ Time Frame: up to 19-20 weeks ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. Pharmacokinetics evaluation [Cmax] [ Time Frame: up to 11-12 weeks ]
  13. Pharmacokinetics evaluation [Tmax] [ Time Frame: up to 11-12 weeks ]
  14. Pharmacokinetics evaluation [AUC] [ Time Frame: up to 11-12 weeks ]
  15. Pharmacokinetics evaluation [T1/2] [ Time Frame: up to 11-12 weeks ]
  16. Pharmacokinetics evaluation [Vd] [ Time Frame: up to 11-12 weeks ]
  17. Pharmacokinetics evaluation [Clearance] [ Time Frame: up to 11-12 weeks ]

Other Outcome Measures:
  1. Change from baseline in oral pain intensity measured by VAS at different time points along the study. [ Time Frame: two times a week up to 19-20 weeks ]
  2. Number (percentage) of patients who need minor or major opioids [ Time Frame: up to 19-20 weeks ]
  3. Number (percentage) of patients who need special procedures on nutritional status (feeding tube, jejunostomy, gastrostomy) [ Time Frame: up to 19-20 weeks ]
  4. Radiotherapy treatment breaks (cause) [ Time Frame: up to 8-10 weeks ]
  5. Radiotherapy treatment breaks (number of days) [ Time Frame: up to 8-10 weeks ]
  6. Total dose and intensity of radiotherapy: Total Gy; [ Time Frame: up to 8-10 weeks ]
  7. Total dose and intensity of radiotherapy: Gy/week; [ Time Frame: up to 8-10 weeks ]
  8. Total dose and intensity of radiotherapy: Gy/day [ Time Frame: up to 8-10 weeks ]
  9. Milligrams of systemic antineoplastic treatment administered (dose intensity: mg/m2/week) [ Time Frame: up to 8-10 weeks ]
  10. Number (percentage) of patients with complete response using the RECIST 1.1 criteria [ Time Frame: 2 months after completion of radiotherapy ]
  11. Number (percentage) of patients with partial response using the RECIST 1.1 criteria [ Time Frame: 2 months after completion of radiotherapy ]
  12. Number (percentage) of patients with stable disease using the RECIST 1.1 criteria [ Time Frame: 2 months after completion of radiotherapy ]
  13. Number (percentage) of patients with progression disease using the RECIST 1.1 criteria [ Time Frame: 2 months after completion of radiotherapy ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female patients 18 years or over.
  2. Patients who gave written informed consent.
  3. Life expectancy ≥ 3 months.
  4. Subjects willing to comply with treatment and follow-up.
  5. Histologically confirmed diagnosis of non-metastatic TNM-2010 stage III-IV squamous cell carcinoma of the following sites:

    • oral cavity
    • 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.

  6. 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.
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
  8. 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

Exclusion Criteria:

  1. Patients with blistering disease.
  2. Patients who require feeding with either nasogastric tube, gastrostomy or jejunostomy at study entry
  3. Patients whose radiotherapy treatment planned dose is lower than 66 Gy
  4. Patients being receiving another investigational agent because of participation in another therapeutic trial
  5. Patients treated with fluvoxamine, estrogens, cimetidine, 5- and 8 methoxypsoralen and/or carbamazepine
  6. Active viral, bacterial or fungal infections of the mouth in the last 14 days (i.e. stomatitis related to herpes virus or candida)
  7. Pregnancy or lactation
  8. Known allergy to melatonin
  9. Prior radiotherapy of the head and neck
  10. Patients with a treatment plan consisting of chemoradiation followed by further chemotherapy
  11. Patients with a diagnostics of a synchronic neoplasia except for non-melanoma skin cancer curable with local treatment or in situ cervix carcinoma
  12. Any investigational agent within 30 days prior to inclusion
  13. 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
  14. 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.
  15. Any other medical condition that would make the patient inappropiate for study participation according to the Investigator's judgement.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02630004


Locations
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Spain
Institut Català d'Oncologia ICO Badalona
Badalona, Barcelona, Spain, 08916
Institut Català d'Oncologia L'Hospitalet
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital Clínico Universitario de Santiago
Santiago de Compostela, La Coruña, Spain, 15706
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08026
Hospital Universitari de la Vall d'Hebron
Barcelona, Spain, 08035
Institut Català d'Oncologia Girona
Girona, Spain, 17007
Hospital San Carlos, Madrid
Madrid, Spain, 28040
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Universitario Virgen de la Victoria
Málaga, Spain, 29010
Hospital Universitario Marqués de Valdecilla
Santander, Spain, 39008
Hospital Miguel Servet
Zaragoza, Spain, 50009
Sponsors and Collaborators
Spherium Biomed
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
Investigators
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Principal Investigator: Alicia Lozano, MD Institut Català d'Oncologia L'Hospitalet
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Responsible Party: Spherium Biomed
ClinicalTrials.gov Identifier: NCT02630004    
Other Study ID Numbers: JAN13004-30
First Posted: December 15, 2015    Key Record Dates
Last Update Posted: March 1, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Spherium Biomed:
Mucositis
Head and Neck cancer
Chemoradiation
Additional relevant MeSH terms:
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Mucositis
Stomatitis
Mouth Diseases
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Stomatognathic Diseases
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants