A Multinational, Multicenter, Open-label, Phase II/III Clinical Trial to Evaluate the Efficacy and Safety of Oral Paclitaxel (DHP107) Compared to IV Paclitaxel as First-line Therapy in Patients with Recurrent or metastatic HER2 negative Breast Cancer

Phase 1

Conditions: Recurrent or metastatic HER2 negative Breast Cancer
MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10006198Term: Breast cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2020-000954-86-BG

Lead Sponsor: Daehwa Pharmaceutical Co., Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 556

Inclusion Criteria

1) Subjects who are = 19 years of age on the date of written informed consent.
2) Subjects with confirmation of primary, recurrent or metastatic HER2 negative breast cancer based on histopathology examination (tumor characteristics should be confirmed by histological or cytological evaluation). However, in case of a metastasis or recurrence, it is not required to be verified again by histopathology, i.e it is possible to register with imaging alone.
(1) Subjects are eligible for the study regardless of hormone receptor status (ER/PR positive or negative).
(2) ER/PR(+) is defined as cells expressing hormone receptors >1% in immunohistochemistry (IHC) analysis of collected samples.
3) HER2-negative from tumor sample (primary or metastatic) is confirmed with one of the followings as NCCN guiline 20197 (HER2 test should be performed using samples of metastatic site, if metastasis is confirmed and samples can be collected from the metastatic lesions.)
(1) HER2 negative by validated immunohistochemistry (IHC) assay:
- IHC 0, 1+
- When IHC 2+, must reflex test with ISH (if same specimen), or order new test with IHC or dual probe in situ hybridization (ISH) (if new specimen available)
(2) HER2 negative by validated dual-probe ISH assay:
- HER2/CEP17 ratio < 2.0 and average HER2 copy number < 4.0 signals/cell
(3) HER2 negative by concurrent IHC and ISH results:
- HER2/CEP17 ratio = 2.0 and average HER2 copy number < 4.0 signals/cell and concurrent IHC 0-1+ or 2+
- HER2/CEP17 ratio < 2.0 and average HER2 copy number = 6.0 signals/cell and concurrent IHC 0-1+
- HER2/CEP17 ratio < 2.0 and average HER2 copy number = 4.0 and <6.0 signals/cell and concurrent IHC 0-1+ or 2+
4) Subjects with life expectancy = 12 weeks
5) Subjects with Eastern Cooperative Oncology Group (ECOG) performance status 0-1
6) Subjects with measurable or evaluable lesions identified by RECIST version 1.1. (However, for phase II study, only subjects with measurable lesions can be enrolled.)
7) Subjects with confirmed adequate hematologic, renal and liver function as follows:
(1) Absolute neutrophil count (ANC) = 1,500/µL
(2) Platelet = 100,000/µL
(3) Hemoglobin = 9.0 g/dL
(4) Serum creatinine = 1.5 X ULN (but, subjects with CrCl or eGFR = 60 mL/min may participate)
(5) Serum calcium level = 12 mg/dL
(6) Total bilirubin = 1.5 X ULN (except for elevated total bilirubin due to Gilbert’s Syndrome)
(7) Liver function tests:
- If there is no evidence of liver metastases: ALT and AST = 2.5 x ULN
- If liver metastases are documented: ALT and AST = 5 x ULN
8) If subjects with central nervous system metastasis who should be stable for more than 4 weeks prior to randomization
(1) If subjects have a history of steroid administration, such patient can participate if he/she have discontinued steroid, or reduce or maintain dexamethasone administration of up to 4mg per day (or equivalent dosage) for more than 4 weeks prior to randomization date.
(2) Brain-imaging should be used to confirm that there are no new lesions and if subjects have symptoms of CNS metastasis, the investigator should use brain-imaging to confirm such case, at the investigator’s discretion.
9) Subjects who understand and are willing to comply with the protocol at the judgment of the investigator
10) Subjects who voluntarily agree to participate in the study and sign the informed consent form

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subj

Exclusion Criteria

1) Subjects expected to have hypersensitivity to active ingredient and any component of this investigational product.
2) Subjects who previously received drugs of taxane class (subjects who administer the last dose of drug of taxane class = 1 year ago as from the randomization day and have recurrence confirmed can be enrolled)
3) Subjects receiving chemotherapy for recurrent or metastatic HER2 negative breast cancer before screening for the study. However, the following subjects should be allowed to participate:
(1) Subjects who had the last administration of adjuvant or neoadjuvant chemotherapy from randomization for prior breast cancer that is not recurrent or metastatic, and its toxic symptoms have disappeared.
(2) ER/PR(+) subjects can be enrolled regardless of lines of endocrine therapy. (Alone or with CDK4/6 inhibitors, or mTOR inhibitors.)
4) Subjects who received radiotherapy within 2 weeks from the randomization day (subjects who have completed local radiotherapy as palliative therapy for the purpose of pain relief for sites (eg, sites of bone metastasis, etc.) other than the target lesion and have recovered from the resulting acute toxicity (eg, bone marrow suppression) can participate.)
5) Subjects with confirmed heart failure of New York Heart Association (NYHA) class 2 or higher, or clinically significant arrhythmia uncontrolled by drug treatments, at the time of study entry.
6) Subjects with confirmed cardiovascular disease (including unstable angina pectoris, myocardial infarction, stroke, and transient ischemic attack) that occurred within 24 weeks prior to study entry, which is deemed to be clinically significant by the investigator
7) Subjects whose left ventricular ejection fraction (LVEF) measured by echocardiogram, MUGA scan, or standard procedures of study site is < lower limit of normal (50%, if the institutional lower limit of normal is not set) within 12 weeks prior to study entry
8) Subjects with uncontrolled hypertension at the time of randomization (SBP > 140 mmHg or DBP > 90 mmHg despite drug treatments)
9) Subjects who have a history of active hepatitis B or C, or hepatobiliary disorders confirmed by medical records or medical examination
[However, the following subjects may participate:
(1) Subjects with Gilbert’s Syndrome, asymptomatic gallstone, liver metastases, or stable chronic liver disease may participate at the discretion of the investigator.
(2) Healthy carriers of hepatitis B who agree on prophylactic antiviral agent during chemotherapy or C virus can participate if HBV-DNA or HCV RNA titer is negative]
10) Those who have been confirmed to be positive for human immunodeficiency virus (HIV) through medical records or medical examination
11) Confirmed neuropathy grade = 2 (based on CTCAE v4.03) at the time of study entry
12) Subjects with confirmed uncontrolled intercurrent disease or condition including significant mental disease or social status which, in the investigator's judgment, may affect compliance with study procedures
13) Subjects with a history of primary malignancy other than breast cancer. However, the subjects should be allowed to participate if:
(1) It has been at least 5 years and they are disease-free since completion of tumor treatment
14) Subjects who are expected to newly start prophylactic use of bisphosphonate or RANKL inhibitor for bone metastasis during clinical study, at the discretion of investigator. (However, subjects on the drug for bone metastasis or osteoporosi

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the efficacy of oral paclitaxel by comparing the progression-free survival (PFS) of treatment with oral paclitaxel and IV paclitaxel in subjects with Recurrent or metastatic HER2 negative breast cancer.;Secondary Objective: To assess oral paclitaxel compared to IV paclitaxel in terms of the following endpoints in subjects with recurrent or metastatic HER2 negative breast cancer:<br>- Objective response rate (ORR)<br>- Overall survival (OS)<br>- Time to treatment failure (TTF)<br>- Disease control rate (DCR)<br>- Quality of life (QoL) as the EQ-5D-3L<br>- Safety<br>;Primary end point(s): Progression-free survival (PFS) ;Timepoint(s) of evaluation of this end point: Progression Free Survival (PFS) will be assessed up to 18 months.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Objective response rate (ORR)<br>- Overall survival (OS)<br>- Time to treatment failure (TTF)<br>- Disease control rate (DCR)<br>- Quality of life (QoL) as the EQ-5D-3L<br>- Safety;Timepoint(s) of evaluation of this end point: - Objective Response Rate (ORR) will be followed every 6 weeks until progression, an expected average of 9 months.<br>- Overall Survival(OS) will be followed until 6 months after the last participant is enrolled, assessed minimum to 18 months.<br>- Time to Treatment Failure(TTF) will be followed through study completion, an expected average of 4.5 year.<br>- Disease Control Rate(DCR)will be followed through study completion, an expected average of 4.5 year.<br>- Quality of life(QoL) will be assessed C1D1, C2D1, C4D1, C7D1, C10D1 (each cycle is 28 days) and study completion, up to 18 months.<br>- Safety will be assessed up to 28 days after last investigational product administration.

Related Trials