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DS-8201a Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]

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ClinicalTrials.gov Identifier: NCT03734029
Recruitment Status : Recruiting
First Posted : November 7, 2018
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:

The reason for this trial is to compare DS-8201a to other treatments being used for HER2-low breast cancer that has spread to other parts of the body.

DS-8201a is a new medicine for breast cancer that has not been approved yet by the Food and Drug Administration. It is made of a drug and an antibody.

Each participant has a 2 out of 3 chance of receiving the new medicine.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Trastuzumab deruxtecan (DS-8201a) Drug: Capecitabine Drug: Eribulin Drug: Gemcitabine Drug: Paclitaxel Drug: Nab-paclitaxel Phase 3

Detailed Description:

This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of DS8201a versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer subjects.

The study is expected to enroll ~360 DS-8201a subjects and ~180 physician's choice subjects:

  • 60 hormone receptor (HR)-negative
  • 240 HR-positive who have had prior therapy with a cyclin-dependent kinase (CDK) 4/6 inhibitor
  • 240 HR-positive who are naive to treatment with CDK 4/6

There will be approximately 161 sites, including but not limited to, North America, Western Europe, and Asia.

There are planned follow-up visits after permanent discontinuation of study treatment to obtain information about subsequent treatment(s) and survival status.

The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 540 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel model, randomized at a 2:1 ratio
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects
Actual Study Start Date : December 27, 2018
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : January 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: DS-8201a
DS-8201a is administered as an intravenous (IV) infusion every 21 days (Q3W), initially for at least 90 minutes, then, if there is no infusion-related reaction, for a minimum of 30 minutes thereafter.
Drug: Trastuzumab deruxtecan (DS-8201a)
A lyophilized powder prepared by dilution for IV infusion at a dose of 5.4 mg/kg
Other Name: Experimental product

Active Comparator: Physician's Choice

Physician's choice comparative therapy will be administered in accordance with the locally approved label. The physician's choice is predefined, prior to randomization, from the following options:

  • Capecitabine
  • Eribulin
  • Gemcitabine
  • Paclitaxel
  • Nab-paclitaxel
Drug: Capecitabine
Administered according to label, as one option for Physician's Choice (determined before randomization)
Other Name: Anti-cancer drug

Drug: Eribulin
Administered according to label, as one option for Physician's Choice (determined before randomization)
Other Name: Anti-cancer Drug

Drug: Gemcitabine
Administered according to label, as one option for Physician's Choice (determined before randomization)
Other Name: Anti-cancer Drug

Drug: Paclitaxel
Administered according to label, as one option for Physician's Choice (determined before randomization)
Other Name: Anti-cancer Drug

Drug: Nab-paclitaxel
Administered according to label, as one option for Physician's Choice (determined before randomization)
Other Name: Anti-cancer Drug




Primary Outcome Measures :
  1. Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) [ Time Frame: within approximately 3 years ]
    PFS based on BICR is defined as the time from randomization to the first objective (radiographic) documentation of disease progression or death.


Secondary Outcome Measures :
  1. PFS based on Investigator Assessment [ Time Frame: within approximately 3 years ]
    PFS based on Investigator Assessment is defined as the time from randomization to the first clinical observation of disease progression or death.

  2. Overall Survival (OS) [ Time Frame: within approximately 3 years ]
    OS is defined as the time from randomization to death

  3. Objective Response Rate (ORR) [ Time Frame: within approximately 3 years ]
    ORR is defined as the percentage of participants who achieved objective CR or PR, confirmed by a second assessment

  4. Duration of Response (DoR), based on BICR and Investigator assessment [ Time Frame: within approximately 3 years ]
    DoR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is the age of majority in their country
  • Has pathologically documented breast cancer that:

    1. Is unresectable or metastatic
    2. Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
    3. Is HR-positive or HR-negative
    4. Has progressed on, and would no longer benefit from, endocrine therapy
    5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the metastatic setting
  • Has documented radiologic progression (during or after most recent treatment)
  • Has adequate tumor samples available or is wiling to provide fresh biopsies prior to randomization for:

    1. assessment of HER2 status
    2. assessment of post-treatment status
  • Has Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
  • Has at least 1 protocol-defined measurable lesion
  • Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions
  • If of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)

Exclusion Criteria:

  • Is ineligible for all options in the physician's choice arm
  • Has breast cancer ever assessed with high-HER2 expression
  • Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate
  • Has uncontrolled or significant cardiovascular disease
  • Has spinal cord compression or clinically active central nervous system metastases
  • Has history, current, or suspicion of interstitial lung disease/pneumonitis
  • Has any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03734029


Contacts
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Contact: (for Asia Sites Only) Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111 (M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp

Locations
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United States, Louisiana
Touro Infirmary Recruiting
New Orleans, Louisiana, United States, 70115
Contact: Principal Investigator    504-894-7115    scott.sonnier@touro.com   
United States, South Carolina
St Francis Hospital Recruiting
Greenville, South Carolina, United States, 29601
Contact: Principal Investigator    864-546-3699    stephen_dyar@bshsi.org   
United States, Texas
BloomTrials Clinical Research, LLC Terminated
Dallas, Texas, United States, 75234
Germany
Rotkreuzklinikum Muenchen gGmbH Not yet recruiting
Muenchen, Bayern, Germany, 80637
Contact: Principal Investigator    +49 8915706621    claus.hanusch@swmbrk.de   
Japan
Aichi Cancer Center Hospital Recruiting
Nagoya, Aichi-Ken, Japan, 464-8681
Contact: See Central Contact         
NHO Kyushu Cancer Center Recruiting
Fukuoka-shi, Fukuoka-Ken, Japan, 811-1395
Contact: See Central Contact         
Hiroshima City Hiroshima Citizens Hospital Recruiting
Hiroshima-shi, Hiroshima-Ken, Japan, 730-8518
Contact: See Central Contact         
Hakuaikai Sagara Hospital Recruiting
Kagoshima, Kagoshima-Ken, Japan, 892-0833
Contact: See Central Contact         
Tokai University Hospital Recruiting
Isehara, Kanagawa-Ken, Japan, 259-1193
Contact: See Central Contact         
Kanagawa Cancer Center Recruiting
Yokohama, Kanagawa, Japan, 241-8515
Contact: See Central Contact         
Cancer Institute Hospital of JFCR Recruiting
Koto-Ku, Tokyo-To, Japan, 135-8550
Contact: See Central Contact         
Showa University Hospital Recruiting
Shinagawa-Ku, Tokyo-To, Japan, 142-8666
Contact: See Central Contact         
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT03734029     History of Changes
Other Study ID Numbers: DS8201-A-U303
2018-003069-33 ( EudraCT Number )
First Posted: November 7, 2018    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc.:
Anti-HER2-Antibody Drug Conjugate (ADC)
Unresectable or Metastatic
Human epidermal growth factor receptor 2 (HER2)-low
DESTINY - Breast 04

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Camptothecin
Albumin-Bound Paclitaxel
Gemcitabine
Capecitabine
Trastuzumab
Antineoplastic Agents
Immunoconjugates
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Topoisomerase I Inhibitors
Topoisomerase Inhibitors