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

This study is currently recruiting participants.
Verified November 2017 by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02564900
First Posted: October 1, 2015
Last Update Posted: December 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )
  Purpose
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 Intervention Phase
Advanced Solid Tumors Drug: DS-8201a Phase 1

Study Type: Interventional
Study Design: 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

Further study details as provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):

Primary Outcome Measures:
  • 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).

  • 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:
  • 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.

  • 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.

  • 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.

  • 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.

  • 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.


Estimated Enrollment: 278
Study Start Date: August 2015
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Baysian 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

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.
  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
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


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

Locations
United States, California
Sharp Memorial Hospital Recruiting
San Diego, California, United States, 92123
Contact: Study Coordinator    858-939-5062    cathy.wood@sharp.com   
United States, Florida
Mayo Clinic Not yet recruiting
Jacksonville, Florida, United States, 32224
Contact: Study Coordinator    904-953-6820    mackowiak.joshua@mayo.edu   
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Study Coordinator    502-632-5717    belma.kantardzic@louisville.edu   
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Study Coordinator    617-632-2403    kellym_silvestri@dfci.harvard.edu   
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Study Coordinator    314-747-5442    w.tate@wustl.edu   
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Study Coordinator    646-888-5342    khoshis@mskcc.org   
United States, Ohio
UC Health Clinical Trials Office Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Study Coordinator    513-584-2951    gajiuta@ucmail.uc.edu   
United States, Texas
University of Texas M. D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030-3721
Contact: Study Coordinator    713-792-2817    cosamuel@mdanderson.org   
Japan
Aichi Cancer Center Hospital Recruiting
Aichi, Japan
National Cancer Center Hospital East Recruiting
Chiba, Japan
Social Medical Corporation Hakuaikai Sagara Hospital Recruiting
Kagoshima, Japan
Kindai University Hospital Recruiting
Osaka, Japan
National Cancer Center Hospital Recruiting
Tokyo, Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research Recruiting
Tokyo, Japan
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Daiichi Sankyo, Inc.
Investigators
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
  More Information

Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT02564900     History of Changes
Other Study ID Numbers: DS8201-A-J101
First Submitted: September 21, 2015
First Posted: October 1, 2015
Last Update Posted: December 4, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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