Phase I Dose Finding Study for Melatonin in Pediatric Oncology Patients With Relapsed Solid Tumors

• Patients must be able to take medication by mouth either by swallowing, chewing or sublingual routes.
• Patients must have a documented life expectancy of ≥ 8 weeks.
• Patients must have histologic or radiographic evidence of a relapsed malignant solid tumor. Intrinsic brain stem tumors or optic pathway gliomas may be diagnosed by clinical and radiologic methods.
• Patient, parent, legal representative and/or guardian must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
• Minimum Weight Requirements: Dose level 1 - 22.2kg, Dose level 2 - 11.1kg, Dose level 3 - 5.6kg
• Patients must be taking a stable dose (with no additions, modifications or deletions) of chemotherapy started ≥ 14 days prior study enrollment.
• Prescribed Chemotherapy drug(s) must not be known to interact with melatonin

• Adequate Bone Marrow Function Defined as:

  1. Patients with solid tumors without bone marrow involvement:

     • Peripheral absolute neutrophil count (ANC) ≥ 1 x109/L
     • Platelet count ≥ 50 X 109/L (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
     • Hemoglobin ≥ 80 g/L (may receive RBC transfusions)

  2. Patients with known bone marrow metastatic disease are eligible for study but not evaluable for hematologic toxicity.

     • Must not be known to be refractory to red cell or platelet transfusions.
     • These patients do not need to meet the bone marrow function requirements, as hematological toxicity will not be measured due to metastatic disease.

• Adequate Liver Function Defined as:

  • Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
  • ALT ≤ 1.5 x ULN for age.

Exclusion Criteria:

• Chemotherapy: Melatonin inhibits the action of doxorubicin
• Growth factors that support white cell number administered ≤ 7 days prior to enrollment.
• Patients requiring corticosteroids who are not on a stable or decreasing dose of corticosteroid for ≥ 14 days.
• Patients prescribed immunosuppressant therapy that is not specifically utilized for chemotherapy purposes. Patient prescribed: Cyclosporine, Mycophenolate Mofetil HCL, Tacrolimus, Sirolimus and Azathioprine should be excluded
• Patients prescribed anti-coagulation therapy (Warfarin, Low Molecular Weight Heparin (LMWH), or System Heparin Therapy)
• Concomitant medications that are known CYP1A2 inhibitors interact with Melatonin.
• Patients prescribed megace, corticosteroids and periactin started ≤ 14 days prior to study enrollment.
• Patients taking the following medications: benzodiazepines, nifedipine, NSAID's, ASA and/or Beta Blockers
• Patients ≤ 7 days post-operative from any surgical procedure.
• Patients with any signs of active post-operative bleeding.
• Patients with an infection that is not responding to anti-microbial therapy.
• Any condition that would negatively impact effective gut absorption and/or swallowing of study medication.
• Patients in the opinion of the investigator may not be able to comply with study protocol requirements
• Patients already receiving melatonin are excluded from the study.
• Allergies to the medicinal and/or non-medicinal ingredients of melatonin which include: Melatonin, Calcium Salicate, Croscarmellose Sodium, IsoMalt, Magnesium Stearate, Microcrystalline Cellulose.
• As melatonin can cause fatigue, patients taking melatonin should refrain from driving or operating machinery within 5 hours of taking the melatonin.