Breast Cancer
Conditions
Keywords
melatonion, chemotherapy induced toxicity
Brief summary
Melatonin is an attractive candidate with anticancer activities previously reported in various preclinical and clinical studies. Melatonin not only involves regulating biological rhythms and endocrine function but also functions in the occurrence, development, and treatment of cancer. There is a number of possible mechanisms by which melatonin may exert its anticancer effects. These mechanisms may include potent antioxidant, immunomodulating, oncostatic, antiproliferative, and estrogen-modulating properties. Regarding the immune-potentiating effects, melatonin increases the activity of lymphocytes, monocyte/ macrophage, and natural killer cells. Melatonin may also exert antiangiogenic and direct apoptotic effects. These activities, except for free-radical scavenging, are believed to be receptor-mediated through Melatonin-1 and Melatonin-2 receptors. Preclinical studies have demonstrated the antitumor effects of melatonin when used alone and enhanced effects for chemotherapy when used in combination. Melatonin has shown positive results in a number of clinical trials on patients with cancer. The effect of melatonin in early stages and locally advanced breast cancer is still questioned. Also the effect of melatonin on the development and severity of various chemotherapy-induced toxicities in breast cancer patients will be investigated.
Interventions
DRUGmelatonin
melatonin 20 mg tablet once daily at bedtime
DRUGPlacebo
Placebo once daily at bedtime
Sponsors
Mansoura University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis with primary invasive breast cancer. 2. Patients eligible for receiving neoadjuvant chemotherapy. 3. Eastern Cooperative Oncology Group (ECOG) performance status from 0 to 2. 4. Adequate bone marrow function (white blood count ≥4,000/mm3, platelet count≥100,000/mm3), liver function (aspartate aminotransferase and alanine aminotransferase ≤ 2.5times the upper limit of normal, serum total bilirubin \< 1.5 mg/dl), renal function (creatinine \< 1.5 mg/dl)
Exclusion criteria
1. Patients with metastatic or non-invasive disease. 2. Patients previously received chemotherapy within one month preceding randomization. 3. Patients who were previously taking melatonin. 4. Hypersensitivity to melatonin. 5. Patients with autoimmune diseases. 6. Pregnancy and lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response type to chemotherapy using Residual Cancer Burden (RCB) index. | At time of surgery after termination of neoadjuvant chemotherapy protocol | Residual Cancer Burden index (RCB) is a validated, continuous index combining primary tumor size, cellularity, and nodal metastasis either pathological complete response or presence of residual tumor ( minimal, moderate, or extensive). The primary outcome is the difference in the mean or median RCB index between intervention and control group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence and density of Tumor Infiltrating Lymphocytes within the tumor tissue. | At time of surgery after termination of neoadjuvant chemotherapy protocol | Difference between study arms regarding presence and density of Tumor Infiltrating Lymphocytes within the tumor tissue. This will reflect tumor's biology and the immune response it elicits. |
| The change in radiological tumor size | At time of surgery after termination of neoadjuvant chemotherapy protocol | The change in radiological tumor size (expressed as the largest diameter) compared between both groups. The tumor size will be obtained from standard bilateral mammography and ultrasound imaging of the breast. |
| The proportion of patients achieving pathologic complete response (RCB-0) after neoadjuvant therapy in each group. | At surgery after completion of neoadjuvant chemotherapy. | — |
| Difference in proportions across RCB categories. | At surgery after completion of neoadjuvant therapy | Comparison of the distribution of RCB categories (0, I, II, III) between intervention and control group. 0: No residual disease, 1: minimal residual disease, II: moderate residual disease, III: Severe residual disease. |
| Incidence and grading of myelosuppression, mucositis, and peripheral sensory neuropathy | throughout the period of neoadjuvant chemotherapy protocol (about 6 months) | Incidence of development and grading of some chemotherapy-induced toxicities (myelosuppression, mucositis, and peripheral sensory neuropathy) will be assessed using National Cancer Institute - Common Terminology Criteria for Adverse Events version 5 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse effects | throughout the period of neoadjuvant chemotherapy protocol (about 6 months) | Any adverse/side effect will be evaluated |
Countries
Egypt
Contacts
Primary ContactMona Mohammed Eltamalawy, Ph.D. in Clinical Pharmacy
Outcome results
None listed