NCT03383692

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2018

Longer than P75 for phase_1

Geographic Reach
3 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 7, 2017

Completed
19 days until next milestone

First Posted

Study publicly available on registry

December 26, 2017

Completed
17 days until next milestone

Study Start

First participant enrolled

January 12, 2018

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 26, 2018

Completed
2.7 years until next milestone

Results Posted

Study results publicly available

June 14, 2021

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 11, 2023

Completed
Last Updated

December 11, 2023

Status Verified

September 1, 2023

Enrollment Period

9 months

First QC Date

December 7, 2017

Results QC Date

May 18, 2021

Last Update Submit

December 7, 2023

Conditions

Neoplasm Metastasis

Keywords

Unresectable or metastatic solid malignant tumorsSolid malignant tumorsOncologyHER2Antibody drug conjugateADC

Outcome Measures

Primary Outcomes (8)

  • Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Ritonavir - Cohort 1

    Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody.

    Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)

  • Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) For MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1

    Maximum concentration (Cmax) was assessed for MAAA-1181a.

    Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)

  • Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Ritonavir - Cohort 1

    Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) for DS-8201a and total anti-HER2 antibody were assessed.

    Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)

  • Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1

    Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a.

    Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)

  • Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Itraconazole - Cohort 2

    Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody.

    Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)

  • Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2

    Maximum concentration (Cmax) was assessed for MAAA-1181a.

    Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)

  • Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Itraconazole - Cohort 2

    Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for DS-8201a and total anti-HER2 antibody.

    Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)

  • Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2

    Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a.

    Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)

Secondary Outcomes (3)

  • Best Objective Response as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors

    Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose

  • Objective Response Ratio (ORR) as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors

    Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose

  • Objective Response Rate as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors

    Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose

Study Arms (2)

Cohort 1: DS-8201a + Ritonavir

EXPERIMENTAL

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-8201aDrug: Ritonavir

Cohort 2: DS-8201a + Itraconazole

EXPERIMENTAL

DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Itraconazole BID on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3

Drug: DS-8201aDrug: Itraconazole

Interventions

DS-8201aDRUG

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

Cohort 1: DS-8201a + RitonavirCohort 2: DS-8201a + Itraconazole
RitonavirDRUG

Ritonavir is a OATP1B inhibitor; an antiretroviral tablet for oral administration

Also known as: Norvir
Cohort 1: DS-8201a + Ritonavir
ItraconazoleDRUG

Itraconazole is a CYP3A inhibitor; an antifungal tablet for oral administration

Also known as: Sporanox, Orungal
Cohort 2: DS-8201a + Itraconazole

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Hokkaido Cancer Center

Sapporo, Hokkaido, 003-0804, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Kobe University Hospital

Kobe, Hyōgo, 650-0017, Japan

Location

Hamamatsu University Hospital

Hamamatsu, Shizuoka, 431-3125, Japan

Location

Shizuoka Cancer Center

Nagaizumicho, Shizuoka, 411-0934, Japan

Location

National Cancer Center Hospital

Chuo Ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR

Koto-Ku, Tokyo, 135-8550, Japan

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (1)

  • Takahashi S, Bando H, Kinoshita I, Modi S, Tsurutani J, Bang YJ, Sato Y, Nakatani S, Lee C, Sugihara M, Okuda Y, Iwata H. Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies. Jpn J Clin Oncol. 2024 Apr 6;54(4):434-443. doi: 10.1093/jjco/hyad181.

    PMID: 38231777DERIVED

MeSH Terms

Conditions

Neoplasm MetastasisNeoplasms

Interventions

trastuzumab deruxtecanRitonavirItraconazole

Condition Hierarchy (Ancestors)

Neoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsTriazolesPiperazines

Results Point of Contact

Title
Contact for Clinical Trial Information
Organization
Daiichi Sankyo
CTRinfo@dsi.com
908-992-6400

Study Officials

  • Global Clinical Leader

    Daiichi Sankyo

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 7, 2017

First Posted

December 26, 2017

Study Start

January 12, 2018

Primary Completion

September 26, 2018

Study Completion

September 11, 2023

Last Updated

December 11, 2023

Results First Posted

June 14, 2021

Record last verified: 2023-09

Data Sharing

IPD Sharing
Will share

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/

Shared Documents
STUDY PROTOCOL, SAP, 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.
More information

Locations

KR(2)JP(7)TW(1)