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

Study Overview
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Brief Summary
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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.

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

Conditions
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Relapsed Malignant Solid Tumor

Intervention / Treatment
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* Drug: Melatonin


Participation Criteria
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Eligibility Criteria
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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: 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) 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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin<br> | Drug: Melatonin<br> <br> * Other names: SISU Melatonin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated daily dose of melatonin. |  | 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of dose limiting toxicities during 8 weeks of melatonin therapy. |  | 8 Weeks | 
| Peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of Melatonin. |  | 8 Weeks | 
| The quantity of cytokines will be measured during 8 weeks of melatonin therapy. |  | 8 Weeks | 
| Change from Baseline in weight after 8 weeks of therapy. |  | 8 Weeks |