Description:
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.
Clinical Trials /
Study of DS-8201a in Subjects With Advanced Solid Malignant Tumors
NCT02564900
Related Conditions:
- Adenocarcinoma of the Gastroesophageal Junction
- Breast Carcinoma
- Gastric Carcinoma
- Malignant Solid Tumor
Recruiting Status:
Active, not recruiting
Phase:
Phase 1
Trial Eligibility
Document
Title
- Brief Title:Study of DS-8201a in Subjects With Advanced Solid Malignant Tumors
- 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
Clinical Trial IDs
- ORG STUDY ID: DS8201-A-J101
- NCT ID: NCT02564900
Trial Conditions
- Advanced Solid Tumors
Trial Interventions
| Drug | Synonyms | Arms |
|---|---|---|
| DS-8201a | Part 1 Dose escalation |
Trial 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.
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|---|---|---|
| Part 1 Dose escalation | Experimental | 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. |
|
| Part 2 Dose expansion | Experimental | 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) |
|
Eligibility 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:
- Advanced 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.
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Both |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | number of subjects experiencing adverse events |
| Time Frame: | Day 1 through 28 days after last dose |
| Safety Issue: | Yes |
| Description: | frequency and seriousness of treatment emergent adverse events (TEAEs). |
Secondary Outcome Measures
| Measure: | change in the area under curve AUC of DS-8201a |
| Time Frame: | from first dose to Day 45 |
| Safety Issue: | No |
| Description: | 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. |
| Measure: | change in the maximum plasma concentration Cmax of DS-8201a |
| Time Frame: | from first dose to Day 45 |
| Safety Issue: | No |
| Description: | 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. |
| Measure: | change in the time of maximum plasma concentration Tmax of DS-8201a |
| Time Frame: | from first dose to Day 45 |
| Safety Issue: | No |
| Description: | 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. |
| Measure: | change in the total anti-HER2 antibody |
| Time Frame: | from first dose to Day 45 |
| Safety Issue: | No |
| Description: | Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15. |
| Measure: | change in MAAA-1181 level |
| Time Frame: | from first dose to Day 45 |
| Safety Issue: | No |
| Description: | 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. |
Trial Keywords
- Advanced solid tumors
- phase 1
- oncology
- HER2
- Antibody drug conjugate (ADC)
