- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03291886
Phase 2 Study of KHK2375 in Subjects With Advanced or Recurrent Breast Cancer
Study of KHK2375 in Subjects With Advanced or Recurrent Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Chiba, Japan
- Chiba Cancer Center
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Fukuoka, Japan
- Kyushu Cancer Center
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Kagoshima, Japan
- Sagara Hospital
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Kumamoto, Japan
- Kumamoto University Hospital
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Kyoto, Japan
- Kyoto University Hospital
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Niigata, Japan
- Niigata Cancer Center Hospital
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Okayama, Japan
- Okayama University Hospital
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Osaka, Japan
- Osaka National Hospital
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Aichi
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Nagoya, Aichi, Japan
- Aichi Cancer Center Hospital
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Nagoya, Aichi, Japan
- Nagoya City University Hospital
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Ehime
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Matsuyama, Ehime, Japan
- Shikoku Cancer Center
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Fukuoka
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Kitakyushu, Fukuoka, Japan
- Kitakyushu Municipal Medical Center
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Gunma
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Ota, Gunma, Japan
- Gunma Cancer Center
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Hokkaido
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Sapporo, Hokkaido, Japan
- Hokkaido University Hospital
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Sapporo, Hokkaido, Japan
- Hokkaido Cancer Center
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Hyogo
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Nishinomiya, Hyogo, Japan
- The Hospital of Hyogo College of Medicine
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Ibaraki
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Tsukuba, Ibaraki, Japan
- Tsukuba University Hospital
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Kanagawa
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Isehara, Kanagawa, Japan
- Tokai University Hospital
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Yokohama, Kanagawa, Japan
- Kanagawa Cancer Center
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Okinawa
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Naha, Okinawa, Japan
- Nahanishi Clinic
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Osaka
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Osakasayama, Osaka, Japan
- Kindai University Hospital
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Suita, Osaka, Japan
- Osaka University Hospital
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Saitama
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Hidaka, Saitama, Japan
- Saitama Medical University International Medical Center
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Tokyo
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Bunkyo, Tokyo, Japan
- Tokyo Metropolitan Cancer and Infectious disease Center Komagome Hospital
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Chuo, Tokyo, Japan
- National Cancer Center Hospital
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Koto, Tokyo, Japan
- The Cancer Institute Hospital of Jfcr
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Minato, Tokyo, Japan
- Toranomon Hospital
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Shinagawa, Tokyo, Japan
- Showa University Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Personally submitted voluntary written informed consent to participate in the study
- Age ≥ 20 years at the time of consent
- Histologically or cytologically confirmed breast cancer positive for estrogen receptor (ER) and/or progesterone receptor (PgR)
- Human epidermal growth factor 2 (HER2)-negative
- Stage III/locally advanced or metastatic carcinoma of the breast where local therapy with curative intent is impossible
Pre/Peri- and postmenopausal women
Postmenopausal status is defined either by:
- Age ≥ 55 years and ≥ 1 year of amenorrhea
- Age < 55 years and ≥ 1 year of amenorrhea, with blood estradiol (E2) < 20 pg/mL
- Age < 55 years with hysterectomy, with ovaries and E2 < 20 pg/mL
- Surgical menopause with bilateral oophorectomy Pre/perimenopausal women may be enrolled only if they agree to receive an luteinizing hormone-releasing hormone (LH-RH) agonist
- Eastern Cooperative Oncology Group(ECOG) performance status (PS) of 0 or 1 at enrollment
- Measurable or nonmeasurable lesions per RECIST version 1.1 criteria
Subjects meeting either of the following criteria:
- History of treatment with a nonsteroidal aromatase inhibitor (AI) for advanced or recurrent breast cancer, and development of progressive disease (PD) after the most recent prior treatment
- No history of treatment with endocrine therapy for advanced or recurrent breast cancer that has recurred during or within 12 months after postoperative adjuvant therapy with an nonsteroidal AI
- An adverse event for which a causal relationship to prior treatment cannot be denied (except alopecia) is Grade ≤ 1 in severity or has returned to the baseline level, i.e., the level before the start of the prior treatment
The latest laboratory values obtained prior to enrollment must meet all of the following requirements:
- Hemoglobin concentration: ≥ 9.0 g/dL
- Platelet count: ≥ 100000/μL
- Neutrophil count: ≥ 1500/μL
- Serum creatinine: ≤ 2.0 mg/dL
- Total bilirubin in serum: < 1.5 × institutional upper limit of normal (≤ 3 mg/dL for subjects with Gilbert's syndrome)
- Aspartate transaminase(AST) and Alanine transaminase(ALT): ≤ 3.0 × institutional upper limit of normal
Exclusion Criteria:
Endocrine therapy (except for LH-RH agonist), treatment with everolimus, treatment with a cyclin-dependent kinase inhibitor, or radiation therapy within 14 days before enrollment
Subjects with prior treatment with exemestane may be enrolled if they meet either of the following criteria:
- Start of treatment with exemestane for advanced or recurrent breast cancer within 28 days before enrollment
- Recurrence-free period >12 months after completion of treatment with exemestane as postoperative adjuvant therapy. For painful bone lesions or impending fractures, radiation therapy may be used concomitantly if there is a measurable or nonmeasurable lesion that is suitable for efficacy evaluation in a region other than the radiation field
- Two or more prior chemotherapy regimens for advanced or recurrent breast cancer
- Chemotherapy within 21 days before enrollment
- Treatment with bisphosphonates or anti-RANKL antibody that is scheduled to be started within 7 days before the first dose of investigational product
- History of or current central nervous system metastasis, or current leptomeningeal or periosteal disease
- History of cancer other than breast cancer within 5 years, or concurrent cancer other than breast cancer (except for basal cell carcinoma of skin, squamous cell carcinoma of skin, and intraepithelial carcinoma of uterine cervix).Subjects continuing to receive treatment for cancer other than breast cancer are ineligible for enrollment
- Ongoing treatment with any other anticancer therapy or investigational product (Except for treatment with exemestane or radiotherapy as described in exclusion criterion 1)
- Prior treatment with histone deacetylase inhibitor (e.g. valproate, vorinostat)
- Known allergy to imidazoles, exemestane, or entinostat
- Any medical or psychiatric condition that could affect compliance with the protocol, ability to give consent, or assessment of anticipated toxicities
- Uncontrolled complications (e.g., active infections)
- Positive for either hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus antibody
- Any other conditions unsuitable for the study in the opinion of the investigator or subinvestigator
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A (exemestane, Entinostat)
5 mg KHK2375 will be administered to subjects once weekly. EXE001 will be administered at a dose of 25 mg once daily orally. Pre/perimenopausal female patients also receive luteinizing hormone-releasing hormone (LH-RH) agonist. |
Given PO
Other Names:
Given PO
Other Names:
|
Placebo Comparator: Arm B (exemestane, Entinostat(placebo))
KHK2375 Placebo will be administered to subjects once weekly. EXE001 will be administered at a dose of 25 mg once daily orally. Pre/perimenopausal female patients also receive luteinizing hormone-releasing hormone (LH-RH) agonist. |
Given PO
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival(PFS) defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1)
Time Frame: Approximately 29 months
|
PFS is defined as the number of days from the date of randomization to the date of first documented progressive disease (PD) or the date of death from any cause, whichever comes first (date of first documented PD or death - date of randomization + 1).
The date of first documented PD is the date when PD is first documented at overall response assessment or the date when overall response other than complete response (CR) and not evaluable (NE) is documented after first CR.
Subjects who receive post-study treatment before the documentation of PD and subjects with no documented PD or death will be censored at the last date they were confirmed to have no PD.
Subjects whose overall response from the date of randomization onward is only NE or who have never undergone assessment of antitumor effect, and whose death has not been documented will be censored at the date of randomization.
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Approximately 29 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: Up to 50 months
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OS is defined as the number of days from the date of randomization to death from any cause (date of death - date of randomization + 1).
Subjects without documented death at the time of data cutoff will be censored at the last date they were confirmed to be alive.
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Up to 50 months
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Antitumor effect
Time Frame: Up to 50 months
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The best overall response is defined as the best response recorded from the start of treatment until progression or recurrence according to the categories ordered as CR > partial response(PR) > stable disease (SD) > PD > NE or CR > Non-CR/non-PD > PD > NE.
A best overall response of CR or PR will be regarded as objective response.
A best overall response of CR, PR, or SD for at least 6 months will be regarded as clinical benefit.
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Up to 50 months
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Plasma concentration of KHK2375
Time Frame: Day 1 of Cycle 1, Day 15 of Cycle 1 , and Day 1 of Cycle 2 (each cycle is 28 days)
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Day 1 of Cycle 1, Day 15 of Cycle 1 , and Day 1 of Cycle 2 (each cycle is 28 days)
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Frequency of subjects with treatment-emergent adverse events
Time Frame: Assessed up to 28 days after study discontinuation
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Assessed up to 28 days after study discontinuation
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Disease Attributes
- Breast Diseases
- Breast Neoplasms
- Recurrence
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Histone Deacetylase Inhibitors
- Exemestane
- Entinostat
Other Study ID Numbers
- 2375-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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