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
- 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
- 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.
- Chemotherapy: Melatonin inhibits the action of doxorubicin
- Growth factors that support white cell number administered ≤ 7 days prior to
- 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
- 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
- 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.