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

Phase 1

Completed

• Conditions: Relapsed Malignant Solid Tumor
• Interventions: Drug: Melatonin

• Registration Number: NCT01858155
• Lead Sponsor: C17 Council

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2013-05-15
• Study First Submitted QC: 2013-05-16
• Study First Posted: 2013-05-21
• Primary Completion: 2017-12
• Study Completion: 2017-12-31
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-29
• Last Update Posted: 2019-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Melatonin	Melatonin	-

Primary Outcome Measures

Name	Time	Method
Maximum tolerated daily dose of melatonin.	8 Weeks

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (5)

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada

Children's & Women's Health Centre of British Columbia; 🇨🇦 Vancouver, British Columbia, Canada

Children's Hospital of Eastern Ontario; 🇨🇦 Ottawa, Ontario, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

CHU Ste-Justine; 🇨🇦 Montreal, Quebec, Canada