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

Neoplasm Metastasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03383692
• Other study ID #: DS8201-A-A104
• Secondary ID: 173790
• Status: Completed
• Phase: Phase 1
• Start date: January 12, 2018
• Est. completion date: September 11, 2023

Study information

• Verified date: September 2023
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 11, 2023
• Est. primary completion date: September 26, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Neoplasms

Intervention

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
• Ritonavir
Ritonavir is a OATP1B inhibitor; an antiretroviral tablet for oral administration
• Itraconazole
Itraconazole is a CYP3A inhibitor; an antifungal tablet for oral administration

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo
Japan	Hamamatsu University Hospital	Hamamatsu	Shizuoka
Japan	Kobe University Hospital	Kobe	Hyogo
Japan	The Cancer Institute Hospital of JFCR	Koto-Ku	Tokyo
Japan	Shizuoka Cancer Center	Nagaizumicho	Shizuoka
Japan	Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo Co., Ltd.	AstraZeneca

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Best Objective Response as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors	Best objective response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Completed response (CR) was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.	Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose
Secondary	Objective Response Ratio (ORR) as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors	Objective response ratio (ORR) was defined as the proportion of participants who achieved CR and PR as assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.	Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose
Secondary	Objective Response Rate as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors	Objective response rate (defined as participants who achieved CR and PR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. ORR with confirmation is Objective Response Rate applying a confirmed response of CR/PR in RECIST version 1.1.	Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose