Clinical trial NCT02630004 (phase 1/phase 2, status: completed)
Conditions: oral mucositis
ICD codes: K12.30, K12.39, K12.33, K12.31, K12.32
Drugs: melatonin oral gel 3%, placebo oral gel
SMILES: COC1=CC2=C(NC=C2CCNC(C)=O)C=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility 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.