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Study of DS-8201a in Subjects With Advanced Solid Malignant Tumors

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ClinicalTrials.gov Identifier: NCT02564900
Recruitment Status : Active, not recruiting
First Posted : October 1, 2015
Last Update Posted : December 21, 2018
Sponsor:
Collaborator:
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Study Description
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Brief Summary:
This is an open-label, two-part, multiple study to evaluate the safety and tolerability of DS-8201a in patients with advanced solid malignant tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: DS-8201a Phase 1

Detailed Description:
This study is one single group of participants in two periods. It is therefore not randomized. The dosage strength will change during the study but all participants will receive the same study drug DS-8201a. So the study is not a true 2 arm study, it is a 2 part study.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 278 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, Two-Part, Multicenter, Non-randomized, Open-label, Multiple Dose First-In-Human Study of DS-8201A, in Subjects With Advanced Solid Malignant Tumors
Study Start Date : August 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019
Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 Dose escalation
Part 1 is a dose escalation to identify the Maximum Tolerated dose (MTD) or the recommended phase 2 dose of DS-8201a guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation with overdose control principal.
 Drug: DS-8201a
Experimental: Part 2 Dose expansion
Part 2 is a dose expansion to examine the safety and efficacy of DS-8201a and it is consist of multiple cohorts: in subjects with trastuzumab emtansine (T-DM1)-treated HER2 overexpressing breast cancer (Part 2a); trastuzumab-treated HER2 overexpressing gastric or gastroesophageal junction adenocarcinoma (Part 2b); HER2 low expressing breast cancer (Part 2c), and HER2 expressing other solid malignant tumor (Part 2d)
 Drug: DS-8201a


Outcome Measures
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Primary Outcome Measures :
  1. Number of subjects experiencing adverse events [ Time Frame: Day 1 through 28 days after last dose ]
    frequency and seriousness of treatment emergent adverse events (TEAEs).

  2. Tumor response using RECIST version 1.1 throughout study [ Time Frame: from randomization date until disease progresses, whichever comes first, up to 30 months ]
    RECIST = Response Evaluation Criteria In Solid Tumors Assessment of tumor response is conducted every 6 weeks in the first 24 weeks and thereafter every 12 weeks until progressive disease to evaluate the efficacy of DS-8201a up to 30 months.


Secondary Outcome Measures :
  1. Change in the area under curve (AUC) of DS-8201a [ Time Frame: from first dose to Day 45 ]
    area under curve AUC at Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.

  2. Change in the maximum plasma concentration (Cmax) of DS-8201a [ Time Frame: from first dose to Day 45 ]
    maximum plasma concentration Cmax at Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.

  3. Change in the time of maximum plasma concentration (Tmax) of DS-8201a [ Time Frame: from first dose to Day 45 ]
    time of maximum plasma concentration Tmax at Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.

  4. Change in the total anti-HER2 antibody [ Time Frame: from first dose to Day 45 ]
    Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.

  5. Change in MAAA-1181 level [ Time Frame: from first dose to Day 45 ]
    determine the change in MAAA-1181 level from first dose to Day 45 at Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.


Eligibility Criteria
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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:

  • Eastern Cooperative Oncology Group performance status( PS) of 0 or 1.
  • Left Ventricular Ejection Fraction (LVEF) ≥ 50%

Part 1:

  • Advanced/unresectable or metastatic breast cancer or gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.

Part 2a:

  • Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
  • Treated with ado-trastuzumab emtansine (T-DM1)

Part 2b:

  • Advanced gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
  • Treated with trastuzumab

Part 2c:

  • Advanced breast cancer with HER2 low expression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.

Part 2d:

  • Satisfy at least one of the following criteria

    1. Advanced/unresectable or metastatic solid malignant tumor with HER2 expression other than breast cancer and gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
    2. Advanced/unresectable or metastatic tumor with HER2 mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.

Part 2e:

  • Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
  • Treated with ado-trastuzumab emtansine (T-DM1) (patients with HER2 overexpression only)

Exclusion Criteria:

  • Has a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia.
  • Has a medical history of myocardial infarction or unstable angina.
  • Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females.
  • Has a medical history of clinically significant lung diseases
Contacts and Locations
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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): NCT02564900


Locations
United States, California
Sharp Memorial Hospital
San Diego, California, United States, 92123
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
UC Health Clinical Trials Office
Cincinnati, Ohio, United States, 45229
United States, Texas
University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States, 77030-3721
Japan
Aichi Cancer Center Hospital
Aichi, Japan
National Cancer Center Hospital East
Chiba, Japan
Social Medical Corporation Hakuaikai Sagara Hospital
Kagoshima, Japan
Kindai University Hospital
Osaka, Japan
National Cancer Center Hospital
Tokyo, Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Tokyo, Japan
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Daiichi Sankyo, Inc.
Investigators
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT02564900     History of Changes
Other Study ID Numbers: DS8201-A-J101
First Posted: October 1, 2015    Key Record Dates
Last Update Posted: December 21, 2018
Last Verified: November 2018
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)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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/

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Advanced solid tumors
phase 1
oncology
HER2
Antibody drug conjugate (ADC)

Additional relevant MeSH terms:
Neoplasms
Camptothecin
Immunoconjugates
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
 Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs