phase i dose finding study for melatonin in pediatric oncology patients with relapsed solid tumors

Conditions: Relapsed Malignant Solid Tumor

Summary: this study will evaluate dose escalation of melatonin in pediatric oncology patients with relapsed solid tumors. the purpose of this study is to determine the safety of melatonin at a dose up to 20 mg daily, as well as to determine the maximum tolerated dose of melatonin.


Eligibility criteria:
inclusion criteria: * 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.