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Study of DS-8201a for Participants With Advanced Solid Malignant Tumors

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03383692
Recruitment Status : Active, not recruiting
First Posted : December 26, 2017
Last Update Posted : July 16, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Brief Summary:

HER2-positive cancer is a cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). HER2 promotes the growth of certain cancer cells. This study will test an experimental drug called DS-8201a that has not been approved by the health authorities yet.

DS-8201a will be tested for safety in patients with advanced solid malignant tumors that test positive for HER2. It also will test how DS-8201a moves within the body (pharmacokinetics).


Condition or disease Intervention/treatment Phase
Neoplasm Metastasis Drug: DS-8201a Drug: Ritonavir Drug: Itraconazole Phase 1

Detailed Description:

The expected time from the first subject's enrollment until the last subject's enrollment is approximately 8.5 months. The screening period is 28 days and each cycle of treatment is 21 days.

The data for the primary analysis will cutoff after all subjects have either discontinued the study or completed at least 3 cycles, whichever comes first. After the primary analysis, the main study will be closed and transition to the extension period.

Depending on the preliminary results of Cohort 1, Sponsor may decide whether Cohort 2 will be opened or not.

The number of treatment cycles is not fixed in this study. Subjects who continue to derive clinical benefit from the study drug in the absence of withdrawal of consent, progressive disease (PD), or unacceptable toxicity may continue the study drug.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open-label, Single Sequence Crossover Study to Evaluate Drug-drug Interaction Potential of OATP1B/CYP3A Inhibitor on the Pharmacokinetics of DS-8201a in Subjects With HER2-expressing Advanced Solid Malignant Tumors
Actual Study Start Date : January 12, 2018
Actual Primary Completion Date : September 26, 2018
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1: DS-8201a + Ritonavir
DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3
Drug: DS-8201a
DS-8201a is provided as a sterile lyophilized powder of DS-8201a in a glass vial, which will be dissolved and administered as an intravenous (IV) solution
Other Name: Experimental product

Drug: Ritonavir
Ritonavir is a OATP1B inhibitor; an antiretroviral tablet for oral administration
Other Name: Norvir

Experimental: Cohort 2: DS-8201a + Itraconazole
DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Itraconazole BID on Day 17 of Cycle 2 until Day 21 of Cycle 3
Drug: DS-8201a
DS-8201a is provided as a sterile lyophilized powder of DS-8201a in a glass vial, which will be dissolved and administered as an intravenous (IV) solution
Other Name: Experimental product

Drug: Itraconazole
Itraconazole is a CYP3A inhibitor; an antifungal tablet for oral administration
Other Names:
  • Sporanox
  • Orungal




Primary Outcome Measures :
  1. Cohort 1: Maximum concentration (Cmax) [ Time Frame: within 3 months ]
    Categories: DS-8201a and MAAA-1181a, with and without ritonavir

  2. Cohort 1: Area under the drug-time concentration curve from 0 to 17 days (AUC0-17d) [ Time Frame: within 3 months ]
    Categories: DS-8201a and MAAA-1181a, with and without ritonavir

  3. Cohort 2: Maximum concentration (Cmax) [ Time Frame: until the end of the trial (approximately 8.5 months) ]
    Categories: DS-8201a and MAAA-1181a, with and without itraconazole

  4. Cohort 2: Area under the drug-time concentration curve from 0 to 17 days (AUC0-17d) [ Time Frame: until the end of the trial (approximately 8.5 months) ]
    Categories: DS-8201a and MAAA-1181a, with and without itraconazole


Secondary Outcome Measures :
  1. Number of participants who discontinued because of adverse events (AEs) [ Time Frame: after all subjects have either discontinued the study or completed at least 4 cycles of the study drug (approximately 8.5 months) ]

    AEs include serious AEs, non-serious treatment-emergent AEs (TEAEs) and AEs of special interest (AESIs)

    Clinically significant changes in physical examination findings, vital sign measurements, standard clinical laboratory parameters, 12-lead electrocardiogram (ECG) parameters, ECHO cardiography or multiple-gated acquisition (MUGA) scan, ophthalmologic findings and anti-drug antibodies will be recorded as AEs.


  2. Objective response rate (ORR) [ Time Frame: through the end of the trial (approximately 8.5 months) ]
    ORR is defined as the percentage of participants who achieve a best overall response of complete response (CR) or partial response (PR)

  3. Disease control rate (DCR) [ Time Frame: through the end of the trial (approximately 8.5 months) ]
    DCR is defined as the percentage of participants who achieve the sum of CR rate, PR rate, and stable disease (SD) rate for a minimum of 5 weeks from the first dosing date

  4. Duration of Response (DoR) [ Time Frame: through the end of the trial (approximately 8.5 months) ]
    DoR is defined as the length of time response of CR or PR or SD lasted

  5. Duration of stable disease (SD) [ Time Frame: through the end of the trial (approximately 8.5 months) ]
    Duration of stable disease is defined as the length of time SD lasted

  6. Clinical benefit ratio (CBR) [ Time Frame: through the end of the trial (approximately 8.5 months) ]
    BR is defined as the number of participants who achieved a best overall response of CR or PR or more than 6 months SD

  7. Time to response (TTR) [ Time Frame: through the end of the trial (approximately 8.5 months) ]
    TTR is defined as the time it took for the participants to have a response

  8. Progression free survival (PFS) [ Time Frame: through the end of the trial (approximately 8.5 months) ]
    Progression-free survival is defined as the length of time the participant survived without the disease getting worse, based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  9. Number of participants with anti-drug antibodies against DS-8201a [ Time Frame: through the end of the trial (approximately 8.5 months) ]
    A reaction to the drug by the immune system leads to production of antibodies against the drug, called an anti-drug antibody (ADA)



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has a pathologically documented unresectable or metastatic solid malignant tumor, with HER2 expression [immunohistochemistry (IHC) 3+, 2+, or 1+ and/or in situ hybridization (ISH) +], Next Generation Sequencing, or other analysis techniques as appropriate] that is refractory to or intolerable with at least one prior systemic chemotherapy regimen, or for which no standard treatment is available
  • Has a left ventricular ejection fraction (LVEF) ≥ 50%
  • Has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1

Exclusion Criteria:

  • Has a contraindication for receiving ritonavir or itraconazole according to the prescribing information
  • Has a medical history of myocardial infarction within 6 months before enrollment or symptomatic congestive heart failure

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): NCT03383692


Locations
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Japan
Hokkaido Cancer Center
Sapporo, Hokkaido, Japan, 003-0804
Hokkaido University Hospital
Sapporo, Hokkaido, Japan, 060-8648
Kobe University Hospital
Kobe, Hyogo, Japan, 650-0017
Hamamatsu University Hospital
Hamamatsu, Shizuoka, Japan, 431-3125
Shizuoka Cancer Center
Nagaizumicho, Shizuoka, Japan, 411-0934
National Cancer Center Hospital
Chuo Ku, Tokyo, Japan, 104-0045
The Cancer Institute Hospital of JFCR
Koto-Ku, Tokyo, Japan, 135-8550
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Samsung Medical Center
Seoul, Korea, Republic of, 06351
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
AstraZeneca
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

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Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT03383692     History of Changes
Other Study ID Numbers: DS8201-A-A104
173790 ( Registry Identifier: JAPIC CTI )
First Posted: December 26, 2017    Key Record Dates
Last Update Posted: July 16, 2019
Last Verified: July 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: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Unresectable or metastatic solid malignant tumors
Solid malignant tumors
Oncology
HER2
Antibody drug conjugate
ADC
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Ritonavir
Itraconazole
Hydroxyitraconazole
Camptothecin
Cytochrome P-450 CYP3A Inhibitors
Immunoconjugates
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 Enzyme Inhibitors
Antifungal Agents
14-alpha Demethylase Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Immunologic Factors