Clinical trial NCT01858155: Phase I Dose Finding Study for Melatonin in Pediatric Oncology Patients With Relapsed Solid Tumors
Official title: Phase I Dose Finding Study for Melatonin in Pediatric Oncology Patients With Relapsed Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed Malignant Solid Tumor
Lead sponsor: C17 Council
Sponsor class: OTHER
First posted: 2013-05-21
Enrollment: 9
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.


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.

Primary outcomes:
measure: Maximum tolerated daily dose of melatonin.
timeFrame: 8 Weeks
Secondary outcomes:
measure: Number of dose limiting toxicities during 8 weeks of melatonin therapy.
timeFrame: 8 Weeks
measure: Peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of Melatonin.
timeFrame: 8 Weeks
measure: The quantity of cytokines will be measured during 8 weeks of melatonin therapy.
timeFrame: 8 Weeks
measure: Change from Baseline in weight after 8 weeks of therapy.
timeFrame: 8 Weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Children's & Women's Health Centre of British Columbia
state: British Columbia
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: CHU Ste-Justine
state: Quebec
Study officials:
affiliation: Children's Hospital of Eastern Ontario
name: Donna Johnston, MD
role: PRINCIPAL_INVESTIGATOR
References: