Management of Severe Chemotherapy-induced Neutropenia in Advanced Breast Cancer
Primary Purpose
Febrile Neutropenia
Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
EC-18
Sponsored by
About this trial
This is an interventional treatment trial for Febrile Neutropenia focused on measuring EC-18, febrile neutropenia, breast cancer, chemotherapy
Eligibility Criteria
Inclusion Criteria:
- Women ≥19 years of age
- Subjects who have voluntarily signed the informed consent prior to the screening tests to participate in the study
- Subjects who have been diagnosed as adenocarcinoma of the breast and relapsed after adjuvant or primary (neoadjuvant) chemotherapy, and thus through history have been confirmed to be candidates for chemotherapy of second line or higher (including hormonal therapy) combined with doxorubicin and cyclophosphamide to treat relapsed or metastatic disease.
Subjects with adequate organ function based on the following clinical laboratory values in the final examination performed within 14 days prior to dosing:
- Neutrophil count (ANC): ≥1,500/mm3
- Platelet count: ≥10.0×104/mm3
- Hemoglobin: ≥9.0 g/dL
- AST, ALT: ≤3.0 x ULN
- Serum total bilirubin: ≤1.5 mg/dL • Serum creatinine: ≤1.5 mg/dL
- Subjects whose Eastern Cooperative Oncology Group (ECOG) performance score is 0-1.
- For women of child bearing potential, subjects should have willingness to use acceptable contraceptive methods during the entire clinical study period.
- Subjects who are capable of understanding the overall procedure of the clinical trial and are willing to participate in compliance with all test procedures.
Exclusion Criteria:
- Subjects with active and inactive hepatitis, patients with HIV, or other uncontrolled infectious disease.
- Subjects who are currently undergoing/receiving antiretroviral therapy due to previous or current immunosuppressive virus infection, hepatitis B surface antigen positive, or positive hepatitis C disease.
- Subjects who received radiation therapy within 4 weeks of dosing.
- Subjects who have been diagnosed within 5 years with other types of cancer except for those who have been appropriately treated for superficial non-melanoma skin cancer or cervical intraepithelial neoplasia.
- Subjects with a history of intolerance for granulocyte colony stimulating factor treatment
- Subjects who are expected to show hypersensitivity to the study drug or its ingredients
- Subjects with a positive urine pregnancy test result prior to the screening visit or the first administration of the study drug
- Subjects who took any other study drug used in a clinical trial within 30 days prior to the screening visit.
- Clinically significant unstable medical abnormality; psychiatric disorder, chronic disease, alcohol or drug use disorder, or other significant biological, psychological, or social factor, which in the investigator's opinion, unfavorably affects the risk-benefit ratio of study participation is likely to interfere with satisfactory study completion or confound its outcome.
- Subjects with unstable heart disease (Example: Congestive heart failure, arrhythmia, symptomatic coronary artery disease); Myocardial infarction within 6 months before initiation of the study.
- Subjects with left ventricular ejection fraction (LVEF) < 50% at screening.
- Significant neurological or psychiatric disorders including dementia or seizures.
- Subjects with poorly controlled hypertriglyceridemia (>500mg/dL) with use of hypolipidemic agents.
- Subjects with poorly controlled diabetes (fasting glucose> 150 mg / dL or HbA1c ≥ 8%).
- Subjects who have received systemic chemotherapy with doxorubicin anticancer agent to treat metastatic or recurrent breast cancer
- Subjects with Grade 2 or higher peripheral sensory neuropathy prior to the screening visit or first dosing of the study drug
- Subjects who have undergone significant gastrectomy with intractable nausea and vomiting, chronic gastrointestinal disease, or clinically significant sequelae, which would interfere with proper absorption of the study drug
- Subjects who were administered with systemic antibiotics within 14 days prior to administration of the study drug
- Subjects whose cumulative dose of doxorubicin exceeds 240 mg/m2'
- Subjects who are currently receiving trastuzumab
Sites / Locations
- National Cancer Center
- Yonsei University Health System Severance Hospital
- Asan Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Cohort 5
Cohort 6
Arm Description
EC-18 500 mg
EC-18 1000 mg
EC-18 1500 mg
EC-18 2000 mg
EC-18 3000 mg
EC-18 4000 mg
Outcomes
Primary Outcome Measures
Duration of Grade 4 neutropenia
Complete blood count and absolute neutrophil count assessed daily to determine febrile neutropenia
Secondary Outcome Measures
Incidence of Grade 3-4 neutropenia
The grade for Neutropenia is assessed according to NCI CTCAE 4.03 version
Incidence of febrile neutropenia
Febrile neutropenia is assessed by ANC and body temperature according to NCI CTCAE version 4.03
Full Information
NCT ID
NCT03104595
First Posted
February 24, 2017
Last Updated
August 13, 2023
Sponsor
Enzychem Lifesciences Corporation
1. Study Identification
Unique Protocol Identification Number
NCT03104595
Brief Title
Management of Severe Chemotherapy-induced Neutropenia in Advanced Breast Cancer
Official Title
EC-18 for Management of Chemotherapy-Induced Neutropenia in Patients With Advanced BC Receiving Low Febrile Neutropenia Risk Chemotherapy: Dose-Escalation, Open-label, Trial to Assess Safety and Tolerability of EC-18
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
October 30, 2017 (Actual)
Primary Completion Date
November 26, 2019 (Actual)
Study Completion Date
December 5, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Enzychem Lifesciences Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
To assess the safety and establish the dose to assess the pharmacokinetic activity following administration of EC-18 in patients with advanced breast cancer receiving low febrile neutropenia risk chemotherapy who are the candidates for second-line or higher combination therapy with doxorubicin and cyclophosphamide.
Detailed Description
This study will utilize a non-randomized, open-label 3 + 3 dose escalation design in which subjects will receive 500 mg, 1000 mg, 1500 mg, 2000 mg, 3000 mg and 4000mg of EC-18. The stepwise daily dosing by cohort was performed for 21 days (3 weeks)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Febrile Neutropenia
Keywords
EC-18, febrile neutropenia, breast cancer, chemotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
3 + 3 dose escalation
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
EC-18 500 mg
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
EC-18 1000 mg
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
EC-18 1500 mg
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
EC-18 2000 mg
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
EC-18 3000 mg
Arm Title
Cohort 6
Arm Type
Experimental
Arm Description
EC-18 4000 mg
Intervention Type
Drug
Intervention Name(s)
EC-18
Other Intervention Name(s)
EC-18 soft capsules
Intervention Description
oral administration
Primary Outcome Measure Information:
Title
Duration of Grade 4 neutropenia
Description
Complete blood count and absolute neutrophil count assessed daily to determine febrile neutropenia
Time Frame
15 days after starting chemotherapy
Secondary Outcome Measure Information:
Title
Incidence of Grade 3-4 neutropenia
Description
The grade for Neutropenia is assessed according to NCI CTCAE 4.03 version
Time Frame
For 15 days after starting chemotherapy (except Day 3 and 4)
Title
Incidence of febrile neutropenia
Description
Febrile neutropenia is assessed by ANC and body temperature according to NCI CTCAE version 4.03
Time Frame
For 15 days after starting chemotherapy (except Day 3 and 4)
Other Pre-specified Outcome Measures:
Title
Incidence of adverse events
Description
Incidence of treatment-emergent adverse events, serious adverse events, adverse events leading to discontinuation, adverse events by severity grade
Time Frame
3-week treatment period and follow-up visit at day 36
Title
Clinical laboratory evaluations
Description
Clinical laboratory tests (hematology, clinical chemistry, coagulation, and urine test result analysis) -- absolute values and changes from the baseline
Time Frame
3-week treatment period and follow-up visit at day 36
Title
Vital signs
Description
Absolute values and changes from baseline in vital signs
Time Frame
3-week treatment period and follow-up visit at day 36
Title
12-lead electrocardiogram (ECG)
Description
Absolute values and changes from baseline ECG
Time Frame
3-week treatment period and follow-up visit at day 36
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Breast cancer
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women ≥19 years of age
Subjects who have voluntarily signed the informed consent prior to the screening tests to participate in the study
Subjects who have been diagnosed as adenocarcinoma of the breast and relapsed after adjuvant or primary (neoadjuvant) chemotherapy, and was confirmed based on documented medical history to be candidates for second-line or higher combination chemotherapy with doxorubicin and cyclophosphamide to treat relapsed or metastatic disease.
Subjects with adequate function of major organs based on the following clinical laboratory values in the latest test performed within 28 days prior to IP dosing:
Neutrophil count (ANC): ≥1,500/mm3
Platelet count: ≥10.0×10^4/mm3
Hemoglobin: ≥9.0 g/dL
AST, ALT: ≤3.0 x ULN
Serum total bilirubin: ≤1.5 mg/dL
Serum creatinine: ≤1.5 mg/dL
Subjects whose Eastern Cooperative Oncology Group (ECOG) performance score is 0-1.
For women of child bearing potential, subjects should have willingness to use acceptable contraceptive methods during the entire clinical study period.
Subjects who are capable of understanding the overall procedure of the clinical study and are willing to participate in compliance with all test procedures.
Exclusion Criteria:
Subjects with active and inactive hepatitis, patients with history of HIV, or other uncontrolled infectious disease.
Subjects with a history of HIV positive or currently undergoing/received antiretroviral therapy, and subjects with a history of hepatitis B surface antigen positive, or current positive hepatitis C disease.
Subjects who received radiation therapy within 4 weeks prior to assignment to treatment group.
Subjects who have been diagnosed within 5 years with other types of cancer except for those who have been appropriately treated for superficial non-melanoma skin cancer or cervical intraepithelial neoplasia.
Subjects with a history of intolerance for granulocyte colony stimulating factor treatment
Subjects who are expected to show hypersensitivity to the IP or its ingredients
Subjects with a positive urine pregnancy test result at screening visit or before the first administration of the study drug
Subjects who took any other investigational product in other clinical study within 30 days prior to screening visit.
Clinically significant unstable medical abnormality; psychiatric disorder, chronic disease, alcohol or drug use disorder, or other significant biological, psychological, or social factor, which in the investigator's opinion, unfavorably affects the risk-benefit ratio of study participation or likely to affect study results.
Subjects with heart disease (i.e. congestive heart failure, arrhythmia, symptomatic coronary artery disease); Myocardial infarction within 6 months before initiation of the study.
Subjects with left ventricular ejection fraction (LVEF) < 50% at screening.
Significant neurological or psychiatric disorders including dementia or seizures.
Patients with dyslipidemia not controlled by drugs [based on LDL-C and TG levels for which treatment is recommended by the Korean dyslipidemia treatment guidelines and the U.S. National Cholesterol Education Program-Adult Treatment Panel III]
Uncontrolled diabetes mellitus (HbA1c >7%; if the level is confirmed after 6 months or longer treatment with oral hypoglycemic agents or insulin)
Subjects who have received systemic chemotherapy with doxorubicin to treat metastatic or recurrent breast cancer
Subjects with grade 2 or higher peripheral sensory neuropathy at screening visit or before the first dosing of the study drug
Subjects who have undergone significant gastrectomy along with intractable nausea and vomiting, chronic gastrointestinal disease, or clinically significant sequelae, which would interfere with proper absorption of the study drug
Subjects who administered systemic antibiotics within 14 days prior to administration of the study drug
Subjects whose cumulative dose of doxorubicin exceeded 240 mg/m2
Subjects who were currently receiving trastuzumab
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sung-Bae Kim, MD, PhD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Center
City
Gyeonggi-do
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Yonsei University Health System Severance Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Management of Severe Chemotherapy-induced Neutropenia in Advanced Breast Cancer
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