Protocol summary

Study aim
Determining the effect of melatonin and comparing it with placebo for the prevention of oxaliplatin-induced neuropathy in patients receiving FOLFOX and XELOX chemotherapy regimens for stage II- IV colorectal cancer
Design
This phase 3 clinical trial will be done on patients with colorectal cancer (stage II to IV) scheduled to undergo FOLFOX or XELOX chemotherapy. 80 patients will enter the study. By random (block-permutation method) 40 patients will receive melatonin and 40 patients will receive placebo every evening. The study will be double-blind, as patient, physician, and the researcher who gathers and analyzes the data will not be informed of patients medication (melatonin or placebo).
Settings and conduct
Allocation to the study groups will be done by one of the researchers who has no role in the treatment and evaluation of the patients, and also analysis of data. Melatonin/placebo treatment will be started on the evening of the first chemotherapy dose and continue through 1 month following the last dose of chemotherapy. Prior to the receiving the first dose of chemotherapy, and at 2 or 3 weeks interval during the course of chemotherapy patient's neurological status will be evaluated. Severity of possible neuropathy will be specified by the mentioned methods.
Participants/Inclusion and exclusion criteria
Inclusion criteria: age ≥18 years old; normal lab values; ability to take part in the study. Exclusion criteria: pre-existing peripheral neuropathy; allergy to drugs; concurrent consumption of drugs effective in preventing or treating neuropathic pain; diabetes.
Intervention groups
Each patient will receive 4 capsules of melatonin or placebo since the first day of starting oxaliplatin-based chemotherapy regimen till the last day of chemotherapy.
Main outcome variables
Percent of grade 2 and 3 neuropathy will be compered among the two study groups.

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20170326033139N1
Registration date: 2018-07-23, 1397/05/01
Registration timing: registered_while_recruiting

Last update: 2018-07-23, 1397/05/01
Update count: 0
Registration date
2018-07-23, 1397/05/01
Registrant information
Name
Raziyeh Kheshti
Name of organization / entity
shiraz university of medical sciences, pharmacy school
Country
Iran (Islamic Republic of)
Phone
+98 71 3225 2705
Email address
kheshti@sums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2018-07-23, 1397/05/01
Expected recruitment end date
2019-05-21, 1398/02/31
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A randomized, placebo controlled, double-blind study of melatonin to prevent oxaliplatin-induced neuropathy in patients receiving FOLFOX and XELOX chemotherapy regimens for stage II- IV colorectal cancer
Public title
Evaluating the possible effect of melatonin on oxaliplatin-induced peripheral neuropathy
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria:
Histologically confirmed stage II-IV colorectal cancers, scheduled to receive oxaliplatin-based chemotherapy (XELOX or FOLFOX with 85 or 130 mg/m2 oxaliplatin every 2 or 3 weeks, respectively ≥18 years of age Eastern Oncology Group (ECOG) Performance Status 0, 1 or 2 The following laboratory values obtained ≤30 days prior to registration: • PLT ≥100,000 • WBC ≥3000 • HgB ≥10 • Total bilirubin ≤1.5 x upper normal limit (UNL) • Serum creatinine ≤1.5 x UNL • AST, ALT ≤ 2.5 x UNL Negative pregnancy test (serum or urine) done ≤ 7 days prior to registration, for women of childbearing potential only Willingness to take part in the study and ability to complete questionnaire by themselves or with assistance and to do study protocol Provide informed written consent, with the right that patients could stop whenever they want
Exclusion criteria:
Pregnancy, lactation or unwilling to employ adequate contraception for women of childbearing potential Prior treatment with neurotoxic chemotherapy such as oxaliplatin, cisplatin, taxanes, or vinca alkaloids Pre-existing peripheral neuropathy (motor or sensory) of any grade A family history of a genetic/familial neuropathy Other medical conditions which, in the opinion of the treating physician, would makes the patient unable to participate in the study (because of safety concerns or noncompliance) Inability to swollow Allergy to oxaliplatin, leucovorin, fluorouracil, capecitabine, melatonin or excipients present in formulation of any of them Concurrent consumption of other medications which are effective in preventing or treating neuropathic pain like carbamazepine, phenytoin, valproic acid, lamotrigin, gabapentin, pregabalin, venlafaxine, duloxetine, tricyclic antidepressants (such as amitryptilline), topical lidocaine, topical capsaicin, supplements like L-Carnitine or vitamin B1 and B6 or any other agent specifically being given to prevent or treat neuropathic pain Diabetes mellitus
Age
From 18 years old
Gender
Both
Phase
3
Groups that have been masked
  • Participant
  • Care provider
  • Investigator
  • Outcome assessor
  • Data analyser
Sample size
Target sample size: 80
Randomization (investigator's opinion)
Randomized
Randomization description
Randomization will be done by block-permutation method, considering 8 blocks, each one consisting 10 patients. Random Allocation software will be used to allocate patients to drug or placebo group. Randomization and allocation will be done by one of the researchers who has no role in the treatment and evaluation of the patients, and also analysis of data.
Blinding (investigator's opinion)
Double blinded
Blinding description
Randomization and allocation will be done by one of the researchers who has no role in the treatment and evaluation of the patients, and also analysis of data. Drug (melatonin) and placebo packaging will be similar and will not be distinguishable by physician and patients who receive them. During the study, melatonin and placebo will be supplied by the same company.
Placebo
Used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics committee of Shiraz University of Medical Sciences
Street address
Zand Blvd.
City
Shiraz
Province
Fars
Postal code
71348-14336
Approval date
2018-06-24, 1397/04/03
Ethics committee reference number
IR.SUMS.REC.1397.275

Health conditions studied

1

Description of health condition studied
Oxaliplatin-induced peripheral neuropathy
ICD-10 code
G62.0
ICD-10 code description
Drug-induced polyneuropathy

Primary outcomes

1

Description
Percent of grade 2 and 3 neuropathy according to National Cancer Institute’s Common Toxicity Criteria for adverse events (NCI-CTCAE V.4) will be compered among the two study groups (case and control), as the main outcome of the study.
Timepoint
Prior to the start of study; during the chemotherapy (prior to receiving each cycle); 1 month after receiving the last dose of chemotherapy or 6 months after initiation of melatonin (each one happens earlier).
Method of measurement
National Cancer Institute’s Common Toxicity Criteria for adverse events (NCI-CTCAE V.4) scale will be used by the oncologist to evaluate severity of neuropathy in the patients. According to this scale severity of neuropathy will be classified from 1 to 5.

Secondary outcomes

1

Description
Patients quality of life according to EORTC QLQ-30 questionnaire will be compared among two groups.
Timepoint
Prior to the start of study; during the chemotherapy (prior to receiving each cycle); 1 month after receiving the last dose of chemotherapy or 6 months after initiation of melatonin (each one happens earlier).
Method of measurement
By the persian version of EORTC QLQ-30 questionnaire

2

Description
Severity of neuropathy according to patients' declaration
Timepoint
Prior to the start of study; during the chemotherapy (prior to receiving each cycle); 1 month after receiving the last dose of chemotherapy or 6 months after initiation of melatonin (each one happens earlier).
Method of measurement
By chemotherapy-induced peripheral neuropathy questionnaire (EORTC CIPN-20) which will be translated to persian language and will be validated prior to study initiation.

3

Description
Severity of neuropathy according to oxaliplatin- specific scale which is evaluated by the physician
Timepoint
Prior to the start of study; during the chemotherapy (prior to receiving each cycle); 1 month after receiving the last dose of chemotherapy or 6 months after initiation of melatonin (each one happens earlier).
Method of measurement
By oxaliplatin- specific scale

Intervention groups

1

Description
Intervention group: Treatment with melatonin will be started on the evening of the first chemotherapy dose and continue through 1 month following the last dose of chemotherapy or 6 months after starting melatonin (each one goes earlier). During this period, patients will consume 20 mg of melatonin (4 capsules, each one contains 5mg melatonin) every evening. Melatonin capsule will be supplied by Zahravi Pharmaceutical Company.
Category
Prevention

2

Description
Control group: Treatment with melatonin will be started on the evening of the first chemotherapy dose and continue through 1 month following the last dose of chemotherapy or 6 months after starting melatonin/placebo (each one goes earlier). During this period, patients will consume 4 capsules of placebo every evening. Placebo capsules will be supplied by Zahravi Pharmaceutical Company and will be the same as melatonin.
Category
Placebo

Recruitment centers

1

Recruitment center
Name of recruitment center
Nemazee Hospital
Full name of responsible person
Mehdi Dehghani
Street address
Nemazee square, Zand Street.
City
Shiraz
Province
Fars
Postal code
71937-11351
Phone
+98 71 3647 4332
Email
nemazee_info@sums.ac.ir
Web page address
http://namazi.sums.ac.ir

2

Recruitment center
Name of recruitment center
Motahari Polyclinic
Full name of responsible person
Mehdi Dehghani
Street address
Nemazee square, Zand Street.
City
Shiraz
Province
Fars
Postal code
71937-11351
Phone
+98 71 3612 1000
Email
motahari@sums.ac.ir
Web page address
http://motahari.sums.ac.ir

3

Recruitment center
Name of recruitment center
Amir Oncology Hospital
Full name of responsible person
Mehdi dehghani
Street address
11th station, Farhangshahr Street
City
Shiraz
Province
Fars
Postal code
71879-15998
Phone
+98 71 3632 3731
Fax
+98 71 3632 5655
Email
amirhp@sums.ac.ir
Web page address
http://amirhp.sums.ac.ir

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Seyyed Basir Hashemi
Street address
Zand street
City
Shiraz
Province
Fars
Postal code
71348-14336
Phone
+98 71 3235 7282
Email
verdep@sums.ac.ir
Web page address
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Shiraz University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic

Person responsible for general inquiries

Contact
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Raziyeh Kheshti
Position
Clinical Pharmacy Resident
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
Alley No. 16, Khalabanan street, Ma'aliabad Street.
City
Shiraz
Province
Fars
Postal code
7187744535
Phone
+98 71 3635 1702
Email
kheshti.raziyeh@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Raziyeh Kheshti
Position
Clinical Pharmacy Resident
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
Alley No. 16, Khalabanan street, Ma'aliabad Street.
City
Shiraz
Province
Fars
Postal code
7187744535
Phone
+98 71 3635 1702
Email
kheshti.raziyeh@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Raziyeh Kheshti
Position
Clinical Pharmacy Resident
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
Alley No. 16, Khalabanan street, Ma'aliabad Street.
City
Shiraz
Province
Fars
Postal code
7187744535
Phone
+98 71 3635 1702
Email
kheshti.raziyeh@yahoo.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Not applicable
Data Dictionary
Not applicable
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