Trial Outcomes & Findings for Melatonin Effect in Combination With Neoadjuvant Chemotherapy to Clinical Response in Locally Advanced Oral Squamous Cell Carcinoma (NCT NCT04137627)
NCT ID: NCT04137627
Last Updated: 2019-12-09
Results Overview
Clinical Response is measured using RECIST 1.1. criteria. CR (Complete response) is defined as disappearance of all target lesion, and pathological lymph node showing reduction of its shortest axis to less than 10 mm. PR (Partial response) is defined as reduction of total target lesion diameter at least by 30%. PD (Progressive disease) is defined as total target lesion diameter increased in size atleast by 20% or 5 mm OR occurence of one new lesion. SD (Stable disease) is defined as absence of reduction or increasing of target lesion. Patients with PR and CR are considered as positive response. Patients with SD and PD are considered as negative response.
COMPLETED
PHASE3
50 participants
1 Year
2019-12-09
Participant Flow
Participant milestones
| Measure |
Melatonin
The group received standard treatment with the oral administration of Melatonin
Melatonin 20 MG Oral Capsule: The administration of Melatonin 20 mg in addition to neoadjuvant chemotherapy to observe the antioxidant and onco-static effect.
|
Placebo
The group received standard treatment with the oral administration of Placebo
Placebo oral capsule: The administration of placebo capsule in addition to neoadjuvant chemotherapy
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
25
|
|
Overall Study
COMPLETED
|
13
|
12
|
|
Overall Study
NOT COMPLETED
|
12
|
13
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Melatonin Group
n=13 Participants
Participants who received Melatonin (treatment arm) who finished study protocol
|
Placebo Group
n=12 Participants
Participants who received Placebo (control arm) who finished study protocol
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Less than or equal to 50 years
|
5 Participants
n=13 Participants
|
7 Participants
n=12 Participants
|
12 Participants
n=25 Participants
|
|
Age, Customized
Greater than 50 years
|
8 Participants
n=13 Participants
|
5 Participants
n=12 Participants
|
13 Participants
n=25 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=13 Participants
|
5 Participants
n=12 Participants
|
10 Participants
n=25 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=13 Participants
|
7 Participants
n=12 Participants
|
15 Participants
n=25 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Indonesia
|
13 Participants
n=13 Participants
|
12 Participants
n=12 Participants
|
25 Participants
n=25 Participants
|
|
Tumor Location
Tongue
|
10 Participants
n=13 Participants
|
9 Participants
n=12 Participants
|
19 Participants
n=25 Participants
|
|
Tumor Location
Buccal
|
1 Participants
n=13 Participants
|
1 Participants
n=12 Participants
|
2 Participants
n=25 Participants
|
|
Tumor Location
Palate
|
0 Participants
n=13 Participants
|
1 Participants
n=12 Participants
|
1 Participants
n=25 Participants
|
|
Tumor Location
Mandible
|
1 Participants
n=13 Participants
|
1 Participants
n=12 Participants
|
2 Participants
n=25 Participants
|
|
Tumor Location
Gingiva (Gum)
|
1 Participants
n=13 Participants
|
0 Participants
n=12 Participants
|
1 Participants
n=25 Participants
|
|
Stage
Stage IV A
|
12 Participants
n=13 Participants
|
10 Participants
n=12 Participants
|
22 Participants
n=25 Participants
|
|
Stage
Stage IV B
|
1 Participants
n=13 Participants
|
2 Participants
n=12 Participants
|
3 Participants
n=25 Participants
|
|
Keratinized/non-keratinized
Keratinized
|
12 Participants
n=13 Participants
|
6 Participants
n=12 Participants
|
18 Participants
n=25 Participants
|
|
Keratinized/non-keratinized
Non-keratinized
|
1 Participants
n=13 Participants
|
6 Participants
n=12 Participants
|
7 Participants
n=25 Participants
|
|
Differentiation
Well Differentiated
|
5 Participants
n=13 Participants
|
4 Participants
n=12 Participants
|
9 Participants
n=25 Participants
|
|
Differentiation
Moderately Differentiated
|
5 Participants
n=13 Participants
|
3 Participants
n=12 Participants
|
8 Participants
n=25 Participants
|
|
Differentiation
Poorly Differentiated
|
3 Participants
n=13 Participants
|
5 Participants
n=12 Participants
|
8 Participants
n=25 Participants
|
|
Grade
High Grade
|
6 Participants
n=13 Participants
|
11 Participants
n=12 Participants
|
17 Participants
n=25 Participants
|
|
Grade
Low Grade
|
7 Participants
n=13 Participants
|
1 Participants
n=12 Participants
|
8 Participants
n=25 Participants
|
|
Medication adherence
Strict adherence
|
10 Participants
n=13 Participants
|
9 Participants
n=12 Participants
|
19 Participants
n=25 Participants
|
|
Medication adherence
Poor adherence
|
3 Participants
n=13 Participants
|
3 Participants
n=12 Participants
|
6 Participants
n=25 Participants
|
PRIMARY outcome
Timeframe: 1 YearClinical Response is measured using RECIST 1.1. criteria. CR (Complete response) is defined as disappearance of all target lesion, and pathological lymph node showing reduction of its shortest axis to less than 10 mm. PR (Partial response) is defined as reduction of total target lesion diameter at least by 30%. PD (Progressive disease) is defined as total target lesion diameter increased in size atleast by 20% or 5 mm OR occurence of one new lesion. SD (Stable disease) is defined as absence of reduction or increasing of target lesion. Patients with PR and CR are considered as positive response. Patients with SD and PD are considered as negative response.
Outcome measures
| Measure |
Melatonin
n=13 Participants
The group received standard treatment with the oral administration of Melatonin
Melatonin 20 MG Oral Capsule: The administration of Melatonin 20 mg in addition to neoadjuvant chemotherapy to observe the antioxidant and onco-static effect.
|
Placebo
n=12 Participants
The group received standard treatment with the oral administration of Placebo
Placebo oral capsule: The administration of placebo capsule in addition to neoadjuvant chemotherapy
|
|---|---|---|
|
Clinical Response as Measured by RECIST 1.1. Criteria
Positive Response
|
5 Participants
|
5 Participants
|
|
Clinical Response as Measured by RECIST 1.1. Criteria
Negative Response
|
8 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: 1 YearExpression of HIF-1⍺ is measured at the initial period of the study (baseline) and after 3 neoadjuvant chemotherapy cycles are completed using qRT-PCR Absolute Quantification. Change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
Outcome measures
| Measure |
Melatonin
n=13 Participants
The group received standard treatment with the oral administration of Melatonin
Melatonin 20 MG Oral Capsule: The administration of Melatonin 20 mg in addition to neoadjuvant chemotherapy to observe the antioxidant and onco-static effect.
|
Placebo
n=12 Participants
The group received standard treatment with the oral administration of Placebo
Placebo oral capsule: The administration of placebo capsule in addition to neoadjuvant chemotherapy
|
|---|---|---|
|
Change in Expression of HIF-1⍺ as Measured by qRT-PCR Absolute Quantification
Pre-Treatment
|
0.018 Picogram/microliter
Interval 0.003 to 0.142
|
0.0048 Picogram/microliter
Interval 0.0005 to 0.254
|
|
Change in Expression of HIF-1⍺ as Measured by qRT-PCR Absolute Quantification
Post-Treatment
|
0.012 Picogram/microliter
Interval 0.0014 to 0.139
|
0.0087 Picogram/microliter
Interval 0.0004 to 0.06
|
|
Change in Expression of HIF-1⍺ as Measured by qRT-PCR Absolute Quantification
Change (Posttreatment - Pretreatment)
|
-0.008 Picogram/microliter
Interval -0.131 to 0.085
|
0.0027 Picogram/microliter
Interval -0.238 to 0.053
|
SECONDARY outcome
Timeframe: 1 YearExpression of miR-210 is measured at the initial period of the study (baseline) and after 3 neoadjuvant chemotherapy cycles are completed using qRT-PCR Absolute Quantification. Change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
Outcome measures
| Measure |
Melatonin
n=13 Participants
The group received standard treatment with the oral administration of Melatonin
Melatonin 20 MG Oral Capsule: The administration of Melatonin 20 mg in addition to neoadjuvant chemotherapy to observe the antioxidant and onco-static effect.
|
Placebo
n=12 Participants
The group received standard treatment with the oral administration of Placebo
Placebo oral capsule: The administration of placebo capsule in addition to neoadjuvant chemotherapy
|
|---|---|---|
|
Change in Expression of miR-210 as Measured by qRT-PCR Absolute Quantification
Pre-Treatment
|
162.8 Picogram/microliter
Standard Deviation 54.92
|
175.2 Picogram/microliter
Standard Deviation 34.3
|
|
Change in Expression of miR-210 as Measured by qRT-PCR Absolute Quantification
Post-Treatment
|
53.8 Picogram/microliter
Standard Deviation 16.65
|
53.5 Picogram/microliter
Standard Deviation 14.28
|
|
Change in Expression of miR-210 as Measured by qRT-PCR Absolute Quantification
Change (Posttreatment - Pretreatment)
|
-109.09 Picogram/microliter
Standard Deviation 51.62
|
-103.71 Picogram/microliter
Standard Deviation 36.24
|
SECONDARY outcome
Timeframe: 1 YearExpression of CD44 is measured at the initial period of the study (baseline) and after 3 neoadjuvant chemotherapy cycles are completed using qRT-PCR Absolute Quantification. Change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
Outcome measures
| Measure |
Melatonin
n=13 Participants
The group received standard treatment with the oral administration of Melatonin
Melatonin 20 MG Oral Capsule: The administration of Melatonin 20 mg in addition to neoadjuvant chemotherapy to observe the antioxidant and onco-static effect.
|
Placebo
n=12 Participants
The group received standard treatment with the oral administration of Placebo
Placebo oral capsule: The administration of placebo capsule in addition to neoadjuvant chemotherapy
|
|---|---|---|
|
Change in Expression of CD44 as Measured by qRT-PCR Absolute Quantification
Pre-Treatment
|
0.0349 Picogram/microliter
Interval 0.0048 to 0.144
|
0.0095 Picogram/microliter
Interval 0.0002 to 0.117
|
|
Change in Expression of CD44 as Measured by qRT-PCR Absolute Quantification
Post-Treatment
|
0.0115 Picogram/microliter
Interval 0.0003 to 0.204
|
0.0187 Picogram/microliter
Interval 0.0012 to 0.278
|
|
Change in Expression of CD44 as Measured by qRT-PCR Absolute Quantification
Change (Posttreatment - Pretreatment)
|
-0.0114 Picogram/microliter
Interval -0.0994 to 0.1736
|
0.0082 Picogram/microliter
Interval -0.1109 to 0.2773
|
SECONDARY outcome
Timeframe: 1 YearExpression of CD133 is measured at the initial period of the study (baseline) and after 3 neoadjuvant chemotherapy cycles are completed using qRT-PCR Absolute Quantification. Change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
Outcome measures
| Measure |
Melatonin
n=13 Participants
The group received standard treatment with the oral administration of Melatonin
Melatonin 20 MG Oral Capsule: The administration of Melatonin 20 mg in addition to neoadjuvant chemotherapy to observe the antioxidant and onco-static effect.
|
Placebo
n=12 Participants
The group received standard treatment with the oral administration of Placebo
Placebo oral capsule: The administration of placebo capsule in addition to neoadjuvant chemotherapy
|
|---|---|---|
|
Change in Expression of CD133 as Measured by qRT-PCR Absolute Quantification
Pre-Treatment
|
1.13 Picogram/microliter
Interval 0.14 to 4.73
|
1.07 Picogram/microliter
Interval 0.04 to 5.64
|
|
Change in Expression of CD133 as Measured by qRT-PCR Absolute Quantification
Post-Treatment
|
1.42 Picogram/microliter
Interval 0.11 to 2.85
|
1.88 Picogram/microliter
Interval 0.22 to 20.9
|
|
Change in Expression of CD133 as Measured by qRT-PCR Absolute Quantification
Change (Posttreatment - Pretreatment)
|
0.43 Picogram/microliter
Interval -3.5 to 1.37
|
0.55 Picogram/microliter
Interval -2.33 to 18.2
|
Adverse Events
Melatonin
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Melatonin
n=13 participants at risk
The group received standard treatment with the oral administration of Melatonin
Melatonin 20 MG Oral Capsule: The administration of Melatonin 20 mg in addition to neoadjuvant chemotherapy to observe the antioxidant and onco-static effect.
|
Placebo
n=12 participants at risk
The group received standard treatment with the oral administration of Placebo
Placebo oral capsule: The administration of placebo capsule in addition to neoadjuvant chemotherapy
|
|---|---|---|
|
Nervous system disorders
Sleep Pattern Disturbance
|
15.4%
2/13 • 56 Weeks
|
16.7%
2/12 • 56 Weeks
|
|
General disorders
Fatigue
|
15.4%
2/13 • 56 Weeks
|
25.0%
3/12 • 56 Weeks
|
|
Nervous system disorders
Headache
|
23.1%
3/13 • 56 Weeks
|
8.3%
1/12 • 56 Weeks
|
|
Nervous system disorders
Decreased Alertness
|
15.4%
2/13 • 56 Weeks
|
0.00%
0/12 • 56 Weeks
|
|
Nervous system disorders
Sleepiness
|
30.8%
4/13 • 56 Weeks
|
25.0%
3/12 • 56 Weeks
|
|
Psychiatric disorders
Emotional Changes
|
15.4%
2/13 • 56 Weeks
|
25.0%
3/12 • 56 Weeks
|
|
Nervous system disorders
Hallucination
|
7.7%
1/13 • 56 Weeks
|
0.00%
0/12 • 56 Weeks
|
Additional Information
Dr. dr. Diani Kartini, Sp.B-K(Onk)
Universitas Indonesia
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place