A Multi-national, Multi-center, Open-label, Phase 2 Clinical Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of DHP107 (Liporaxel®, Oral Paclitaxel) Compared to IV Paclitaxel in Patients with Recurrent or Metastatic 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: EUCTR2020-000960-52-CZ
• Lead Sponsor: Daehwa Pharmaceutical Co., Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-07-29
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

1.Subjects who are =18 years of age on the date of written informed consent.
2.Subjects with confirmed diagnosis of recurrent or metastatic breast cancer based on histopathology examination (tumor characteristics should be confirmed by histological or cytological evaluation):
1)Subjects are eligible for the study regardless of hormone receptor status (ER/PR-positive or -negative)
2)ER/PR-positivity is defined as >1% cells expressing hormone receptors from the metastatic or primary site based on immunohistochemistry (IHC).
3.Subjects with diagnosis of HER2-negative breast cancer that was confirmed by IHC or in situ hybridization (ISH) assessment of tumor samples (from primary or metastatic site) in any of the following cases (If metastasis is confirmed and it is feasible to obtain the tumor sample from the metastatic site, HER2 status assessment must be performed using the sample from the metastatic site):
1)IHC Assessment
•IHC score of 0 or 1+
•In case of IHC score of 2+, ISH must be performed to confirm HER2-negative breast cancer
2)ISH Assessment
•Dual-probe HER2/CEP17 ratio <2 and average HER2 copy number of <6.0 signals per cell.
•Single-probe testing with an average HER2 copy number between 4-6 should be repeated with dual-probe testing.
4.Subjects who have received up to 3 lines of chemotherapy for advanced disease. Surgery, radiotherapy, and endocrine (hormone) therapy are not counted as line of therapy.
5.Subjects who have a life expectancy of =12 weeks.
6.Subjects who are able to take oral medication.
7.Subjects who have a performance status of =2 on the Eastern Cooperative Oncology Group (ECOG) scale.
8.Subjects who have measurable disease according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST version 1.1).
9.Subjects who have adequate organ functions as indicated by the following laboratory values:
•Absolute neutrophil count (ANC) = 1.5 x 109/L;
•Platelet = 100 x 109/L;
•Hemoglobin = 9 g/dL;
•Serum creatinine = 1.5 x institutional ULN (however, a subject who has a CrCl or eGFR = 60 mL/min is eligible);
•Serum total bilirubin =1.5 X ULN (however, higher bilirubin levels due to Gilbert’s syndrome are allowed);
•Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN (or = 5 x ULN for patients with liver metastases).
10.Subjects who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and procedures.
11.Subjects who have voluntarily agreed to participate by giving written informed consent.
12.Women of childbearing potential who have negative pregnancy test results at the screening visit and men with female partners of childbearing potential must agree to use highly effective contraception from the time of providing informed consent until 90 days after last dose of study drug. For female subjects, a double-barrier method of contraception, such as contraceptive cap (vaginal diaphragm or cervical caps for contraception), intra uterine devices (IUDs), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion is accepted; for male subjects, a condom with spermicide or total abstinence is accepted. Use of oral contraceptives is not allowed as a method of birth control.
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 subjects for this age range 72
F.1.3 Elderly (>=65 years) ye

Exclusion Criteria

1.Subjects who have history of severe hypersensitive reaction to the active ingredient or any excipients of DHP107 or IV paclitaxel.
2.Subjects who have received prior taxane therapy in the metastatic setting. However, 1) subjects who received taxane therapy >12 months prior to study entry and 2) did not have disease progression while on taxane, can be eligible for the study.
3.Subjects whose adjuvant or neoadjuvant treatment for early stage breast cancer was completed within 6 months prior to entry into the study.
4.Subjects who received radiation therapy within 2 weeks of randomization (however, subjects who completed local radiation therapy as palliative care to alleviate pain from non-target lesions [e.g., sites of bone metastasis] and recovered from relevant acute toxicity [e.g., bone marrow suppression] are eligible for the study).
5.Subjects who were diagnosed with New York Heart Association (NYHA) Class II congestive heart failure or have clinically significant arrhythmia not controlled by medication prior to study entry.
6.Subjects who developed cardiovascular disease (unstable angina, myocardial infarction, stroke, and transient ischemic attack) within 24 weeks prior to study entry, which is deemed to be clinically significant by the Investigator.
7.Subjects with known active hepatitis B or C infection, or hepatobiliary disease, or known history of immunodeficiency virus infection (However, subjects with Gilbert’s Syndrome, asymptomatic gallstones, or stable chronic liver disease are, at the discretion of the investigator, eligible for the study. Subjects who are hepatitis B carriers may be eligible if they are on antiviral therapy 2 weeks prior to study entry).
8.Subjects with neuropathy grade =2 based on CTCAE v4.03 at the time of study entry.
9.Subjects with uncontrolled medical or mental illness that, in the Investigator’s judgement, could affect treatment tolerability or compliance.
10.Subjects diagnosed with other malignant primary tumor with the exception of the following:
•Malignancy diagnosed at least 5 years previously without evidence of recurrence or persistent disease.
•The complete excision of basal/squamous cell carcinoma or papillary thyroid carcinoma or the complete treatment of cervical intraepithelial neoplasia or other in situ carcinoma.
11.Subjects with symptomatic, untreated metastases to the central nervous system (CNS) at the time of screening. Subjects with treated CNS metastases that are documented to be stable by CT or MRI imaging 4 weeks after completion of radiation and who do not require systemic corticosteroids are eligible.
12.Subjects who are currently receiving (or unable to stop use the day before the first dose of DHP107 and throughout the study) prescription or non prescription medications or other products known to be moderate or potent inhibitors/inducers of CYP3A4, P-gp, or CYP2C8.
13.Subjects who cannot tolerate oral administration as determined by the Investigator including the following:
•Subjects with innate or acquired serious or uncontrolled gastrointestinal disease
•Subjects with bowel obstruction or inflammatory bowel disease (e.g., Crohn’s disease, chronic inflammation) that could affect the administration and absorption of oral medication
•Subjects with uncontrolled diarrhea (e.g., Grade 4 = diarrhea or Grade 3 = diarrhea which lasts for 7 days or more, even when symptomatic therapy is performed)
14.Pregnant or breastfeeding women
15.Subjects who have received any inv

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified