A Clinical Trial to evaluate the Efficacy and Safety of of Oral Paclitaxel (DHP107) Compared to IV Paclitaxel as First-line Therapy in Patients with Recurrent or Metastatic HER2 Negative Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daehwa Pharmaceutical Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Oct 2020 → ongoing

Decision date (initial)

2024-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517090-24-00

EudraCT number

2020-000954-86

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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 objectives 1

1. To assess oral paclitaxel compared to IV paclitaxel in terms of the following endpoints in subjects with recurrent or metastatic HER2 negative breast cancer: - Objective response rate (ORR) - Overall survival (OS) - Time to treatment failure (TTF) - Disease control rate (DCR) - Quality of life (QoL) as the EQ-5D-3L - Safety

Conditions and MedDRA coding

Recurrent or Metastatic HER2 Negative Breast Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1) Subjects who are ≥ 19 years of age on the date of written informed consent.
2. 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. 3) HER2-negative from tumor sample (primary or metastatic) is confirmed with one of the followings as NCCN guideline 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. 4) Subjects with life expectancy ≥ 12 weeks
5. 5) Subjects with Eastern Cooperative Oncology Group (ECOG) performance status 0-1
6. 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. 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. 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 brainimaging to confirm such case, at the investigator’s discretion.
9. 9) Subjects who understand and are willing to comply with the protocol at the judgment of the investigator
10. 10) Subjects who voluntarily agree to participate in the study and sign the informed consent form

Exclusion criteria 19

1. 1) Subjects expected to have hypersensitivity to active ingredient and any component of this investigational product.
2. 10) Those who have been confirmed to be positive for human immunodeficiency virus (HIV) through medical records or medical examination
3. 11) Confirmed neuropathy grade ≥ 2 (based on CTCAE v4.03) at the time of study entry
4. 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
5. 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
6. 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 osteoporosis just before the IP administration can participate and are permitted for concomitant administration during the study. But in that case, the same Dose and Usage should be maintained during the clinical trial period).
7. 15) Subjects determined inappropriate to orally administer the IP at the time of study participation based on the investigator's judgment (1) Clinically significant or uncontrolled congenital or acquired gastrointestinal disease (2) Subjects with confirmed diseases that may interfere with the IP's administration, transfer to digestive tract, or absorption including ileus and inflammatory bowel disease (Crohn’s disease and ulcerative colitis)
8. 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)
9. 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.)
10. 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.)
11. 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.
12. 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
13. 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
14. 8) Subjects with uncontrolled hypertension at the time of randomization (SBP > 140 mmHg or DBP > 90 mmHg despite drug treatments)
15. 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]
16. 16) Pregnant or breast-feeding women
17. 17) Subjects of childbearing women and men (including partners) who are unwilling to remain abstinent nor use adequate contraception during the study and at least 12 weeks after the end of treatment
18. 18) Subjects who have participated in other clinical trials/studies within 2 weeks prior to the administration of this IP or who are scheduled to participate in other clinical trials/studies during this clinical trial period. (However, if the subject participated in control arm of active drug with market approval, he/she can be allowed by investigator’s discretion. Also, subjects who participated in an observational study with minimal medical intervention (e.g. blood or urine test) can also be allowed by investigator’s discretion.)
19. 19) Subjects who are unable to participate in the study at the discretion of investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS)

Secondary endpoints 5

1. Objective Response Rate (ORR)
2. Overall survival (OS)
3. Time to treatment failure (TTF)
4. Disease Control Rate (DCR)
5. EQ-5D-3L

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daehwa Pharmaceutical Co. Ltd.

Sponsor organisation

Daehwa Pharmaceutical Co. Ltd.

Address

495 Hanu-Ro, Hoengseong-Eup Hoengseong-Eup

City

Hoengseong

Postcode

25228

Country

Korea, Republic of

Scientific contact point

Organisation

Daehwa Pharmaceutical Co. Ltd.

Contact name

Minho Jeong

Public contact point

Organisation

Daehwa Pharmaceutical Co. Ltd.

Contact name

Minho Jeong

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications