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

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.

Study Overview

• Status: Completed
• Conditions: Relapsed Malignant Solid Tumor
• Intervention / Treatment: Drug: Melatonin

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's & Women's Health Centre of British Columbia
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Ste-Justine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melatonin	Drug: Melatonin; Other Names: SISU Melatonin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: C17 Council
• Investigators: Principal Investigator: Donna Johnston, MD, Children's Hospital of Eastern Ontario

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: May 15, 2013
• First Submitted That Met QC Criteria: May 16, 2013
• First Posted (Estimate): May 21, 2013

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: C17 MEL P1