Clinical Study of Decitabine and Paclitaxel Combination Therapy

Study Overview
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Brief Summary
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Phase Ib clinical study of Decitabine and Paclitaxel combination therapy

Detailed Description
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An open-labelled, parallel, multiple ascending dose, phase Ib clinical study of Decitabine and Paclitaxel combination therapy in treating patients with metastatic and locally advanced breast cancer

Official Title
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An Open-labelled, Parallel, Multiple Ascending Dose, Phase Ib Clinical Study of Decitabine and Paclitaxel Combination Therapy in Treating Patients With Metastatic and Locally Advanced Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: Decitabine
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 19 years as female be unable to operate for therapy with HER2 negative breast adenocarcinoma and metastatic breast cancer, one or more chemotherapy according to RECIST ver.1.1, one or more evaluable lesion Eastern cooperative oncology group(ECOG) performance score is o or 1 lesion for core biopsy Within 28days of planned first study treatment day, laboratory safety test is satisfied. ANC ≥1500cells/microliter, Platelet count ≥ 100,000 cells/microliter, Hemoglobin≥8.5g/dl, ALT and AST ≤ 2ULN, ALP≤2.5ULN, Serum total bilirubin≤1.25 ULN, PT-INR and aPTT≤1.5ULN, Creatinine≥50ml/min menopause or informed that effective contraception must be used during the entire treatment period of this study and for 6 months after exiting from the study Given signed and dated written informed consent form Exclusion Criteria: Symptomatic metastasis and Leptomeningeal metastasis Injection of paclitaxel for metastatic breast cancer within 6 months HER2, Positive Breast adenocarcinoma cancertherapy for whole body within 3 weeks radiotherapy for metastatic region within 4 weeks major surgery, open biopsy and trauma within 4 weeks less than 4 weeks post major surgery treatment with consistently systemic corticosteroid or immunosuppressive drug more than 2 grade for peripheral neuropathy Congenital ling QT syndrome or QTc interval > 480 milisecond occur myocardial infartion within 6 months unstable angina pectoris HIV(+) or AIDS HBsAg(+) or HCV(+) treatment bisphosphonate for hypercalcemia except metastatic and locally advanced breast cancer, personal history with malignancy within 5 years hypersensitivity reaction with paclitaxel or Cremophor EL formulation Pregnant or breast feeding be unable or unwilling to abide by the study protocol or to cooperate fully with the investigator or designee

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Decitabine<br>A standard 3+3 trial design will be used for Decitabine dose escalation cohorts. The number of cohorts is three. The subjects will be administered Decitabine on every seven days in a 28day cycle and Decitabine is sequential administered with Paclitaxel. Cohort 1: Decitabine 15mg/m2, Cohort 2: Decitabine 20mg/m2, Cohort 3: Decitabine 25mg/m2 | Drug: Decitabine<br>* The subjects will be sequential administered with Decitabine and paclitaxel 80mg/m2 by IV(intravenous) infusion. Decitabine is starting dose of 15mg/m2 on 1D, 8D, 22D, 28D of a 28day cycle. Paclitaxel 80mg/m2 will be dosed in combination therapy with Decitabine on 8D, 22D, 28D of a 28day cycle.<br>* Other names: DW1018;Drug: Paclitaxel<br>* The subjects will be sequential administered with Decitabine and paclitaxel 80mg/m2 by IV(intravenous) infusion. Decitabine is starting dose of 15mg/m2 on 1D, 8D, 22D, 28D of a 28day cycle. Paclitaxel 80mg/m2 will be dosed in combination therapy with Decitabine on 8D, 22D, 28D of a 28day cycle.<br>* Other names: combination therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerant Dose (MTD) and Dose Limiting Toxicity (DLT) | According to principle of Dose Limited Toxicity (DLT) assessment by National Cancer Institute Common Terminonlgy Criteria for Adverse Events (NCI-CTCAE, V4.0), DLT is evaluated above grade 3 as adverse event. | for about 4 weeks |