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Advanced or Recurrent Breast CancerPhase 2NCT03291886

Phase 2 Study of KHK2375 in Subjects With Advanced or Recurrent Breast Cancer

A Phase 2 study testing Entinostat and Exemestane in people with Advanced or Recurrent Breast Cancer, run by Kyowa Kirin Co., Ltd. at 28 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary objective of this study is to investigate the effect of 5 mg KHK2375 on progression free survival (PFS) when administered orally at weekly intervals in combination with exemestane in a placebo-controlled, double-blind comparative study in subjects with advanced or recurrent hormone receptor-positive breast… Read more about this study

Who is it for?
Ages 20 years and older, women only
Conditions the study is for
Advanced or Recurrent Breast Cancer
What is being tested?
Entinostat and Exemestane
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
133 participants
Where
28 sitesJapan
Study dates
22 Sep 2017to 26 Mar 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

Japan28 sites

  • Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital

    Bunkyo, Tokyo

  • Chiba Cancer Center

    Chiba

  • National Cancer Center Hospital

    Chūō, Tokyo

  • Kyushu Cancer Center

    Fukuoka

  • Saitama Medical University International Medical Center

    Hidaka, Saitama

  • Tokai University Hospital

    Isehara, Kanagawa

  • Sagara Hospital

    Kagoshima

  • Kitakyushu Municipal Medical Center

    Kitakyushu, Fukuoka

  • The Cancer Institute Hospital of JFCR

    Koto, Tokyo

  • Kumamoto University Hospital

    Kumamoto

  • Kyoto University Hospital

    Kyoto

  • Shikoku Cancer Center

    Matsuyama, Ehime

  • Toranomon Hospital

    Minato, Tokyo

  • Aichi Cancer Center Hospital

    Nagoya, Aichi-ken

  • Nagoya City University Hospital

    Nagoya, Aichi-ken

  • Nahanishi Clinic

    Naha, Okinawa

  • Niigata Cancer Center Hospital

    Niigata

  • The Hospital of Hyogo College of Medicine

    Nishinomiya, Hyōgo

  • Okayama University Hospital

    Okayama

  • Osaka National Hospital

    Osaka

  • Gunma Cancer Center

    Ōta, Gunma

  • Hokkaido Cancer Center

    Sapporo, Hokkaido

  • Hokkaido University Hospital

    Sapporo, Hokkaido

  • Kindai University Hospital

    Sayama, Osaka

  • Showa University Hospital

    Shinagawa, Tokyo

  • Osaka University Hospital

    Suita, Osaka

  • Tsukuba University Hospital

    Tsukuba, Ibaraki

  • Kanagawa Cancer Center

    Yokohama, Kanagawa

Other trials in Japan

About this study

Official title: Study of KHK2375 in Subjects With Advanced or Recurrent Breast Cancer

The primary objective of this study is to investigate the effect of 5 mg KHK2375 on progression free survival (PFS) when administered orally at weekly intervals in combination with exemestane in a placebo-controlled, double-blind comparative study in subjects with advanced or recurrent hormone receptor-positive breast cancer. The secondary objectives are to investigate the effect of on overall survival (OS) and the antitumor effect and to evaluate the pharmacokinetics and safety.

Being tested
Entinostat, Entinostat(Placebo), Exemestane
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EntinostatDrug

    Also called KHK2375, MS-275, SNDX-275

    Given PO

  • Entinostat(Placebo)Drug

    Also called KHK2375, MS-275, SNDX-275

    Given PO

  • ExemestaneDrug

    Also called EXE001, Aromasin, FCE-24304

    Given PO

Study groups in NCT03291886
Study groupRoleWhat they receive
Arm A (exemestane, Entinostat)Experimental5 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.
Receives: Drug: Entinostat; Drug: Exemestane
Arm B (exemestane, Entinostat(placebo))Placebo comparatorKHK2375 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.
Receives: Drug: Entinostat(Placebo); Drug: Exemestane

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival(PFS) defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1)

    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.

    Measured: Approximately 29 months

Secondary outcomes (2)

  1. Overall survival (OS)

    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.

    Measured: Up to 50 months

  2. Antitumor effect

    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.

    Measured: Up to 50 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2017
  2. Study start22 Sep 2017
  3. Primary completion4 Apr 2019
  4. Study completion26 Mar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double-blinded, randomized trial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
133 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03291886
Sponsor's protocol ID
2375-002
Status last verified
Jun 2022
First submitted
14 Sep 2017
Last updated
21 Jun 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Iwata H, Nakamura R, Masuda N, Yamashita T, Yamamoto Y, Kobayashi K, Tsurutani J, Iwasa T, Yonemori K, Tamura K, Aruga T, Tokunaga E, Kaneko K, Lee MJ, Yuno A, Kawabata A, Seike T, Kaneda A, Nishimura Y, Trepel JB, Saji S. Efficacy and exploratory biomarker analysis of entinostat plus exemestane in advanced or recurrent breast cancer: phase II randomized controlled trial. Jpn J Clin Oncol. 2023 Jan 6;53(1):4-15. doi: 10.1093/jjco/hyac166.

    PubMed 36398439

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Entinostat and Exemestane in people with Advanced or Recurrent Breast Cancer, run by Kyowa Kirin Co., Ltd. at 28 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival(PFS) defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) (time frame: Approximately 29 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03291886, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2022.

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