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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02252211




Registration number
NCT02252211
Ethics application status
Date submitted
22/09/2014
Date registered
30/09/2014

Titles & IDs
Public title
Safety and Bioimaging Trial of DS-8895a in Patients With Advanced EphA2 Positive Cancers
Scientific title
A Phase I Safety and Bioimaging Trial of DS-8895a in Patients With Advanced or Metastatic EphA2 Positive Cancers
Secondary ID [1] 0 0
LUD2014-002
Universal Trial Number (UTN)
Trial acronym
LUD2014-002
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Solid Tumor 0 0
Metastatic EphA2 Positive Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DS-8895a 1 mg/kg
Treatment: Drugs - DS-8895a 3 mg/kg
Treatment: Drugs - DS-8895a 10 mg/kg

Experimental: DS-8895a - Patients received infusions with DS-8895a on Days 1, 8, 22, and 36. Infusions on Days 1 and 36 were trace labelled with \^89Zr (\^89Zr-Df-DS-8895a). The Day 1 dose was 0.2 mg/kg, followed by subsequent doses calculated based on individual patient body weight and dosing cohort assignment.


Treatment: Drugs: DS-8895a 1 mg/kg
Patients received infusions with \^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and \^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.

Treatment: Drugs: DS-8895a 3 mg/kg
Patients received infusions with \^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and \^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.

Treatment: Drugs: DS-8895a 10 mg/kg
Patients were to receive infusions with \^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 10 mg/kg on Days 8 and 22, and \^89Zr-Df-DS-8895a at a dose of 10 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Patients With Treatment-emergent Adverse Events
Timepoint [1] 0 0
Continuously for up to 58 weeks
Secondary outcome [1] 0 0
Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a
Timepoint [1] 0 0
Up to Day 43
Secondary outcome [2] 0 0
Number of Patients With Best Overall Tumor Response
Timepoint [2] 0 0
Up to 58 weeks
Secondary outcome [3] 0 0
Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion
Timepoint [3] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [4] 0 0
Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion
Timepoint [4] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [5] 0 0
Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion
Timepoint [5] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [6] 0 0
Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion
Timepoint [6] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [7] 0 0
Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion
Timepoint [7] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [8] 0 0
Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion
Timepoint [8] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [9] 0 0
Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion
Timepoint [9] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [10] 0 0
Mean Total Serum Clearance of DS-8895a Following the First Infusion
Timepoint [10] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [11] 0 0
Mean Maximum Serum Concentration of DS-8895a Following the First Infusion
Timepoint [11] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [12] 0 0
Mean Elimination Half-life of DS-8895a Following the First Infusion
Timepoint [12] 0 0
Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
Secondary outcome [13] 0 0
Number of Patients With Pharmacodynamic (Metabolic) Response
Timepoint [13] 0 0
Day 29 and Day 50
Secondary outcome [14] 0 0
Number of Patients With Human Anti-Human Antibody Positivity
Timepoint [14] 0 0
Up to 43 Weeks

Eligibility
Key inclusion criteria
1. Advanced or metastatic EphA2 positive cancer (based on immunohistochemistry of archived or fresh tumor tissue).
2. Malignant tumor that was refractory to standard treatment.
3. At least one reference tumor > 1 cm in size for assessment of tumor uptake of ^89Zr-Df-DS-8895a.
4. Expected survival of at least 3 months.
5. Eastern Cooperative Oncology Group performance status = 1.
6. Within the last week prior to the first study drug administration, laboratory parameters for vital functions were to be in the normal range. Out-of-range values that were not clinically significant were permitted, except that the following parameters were to be in the specified ranges:

* Neutrophil count = 1.5 x 10^9/L
* Platelet count = 90 x 10^9/L
* International normalized ratio = 1.5
* Serum aspartate aminotransferase and alanine aminotransferase = 2.5 x the upper limit of normal (ULN); = 5 x ULN if liver metastases
* Serum bilirubin = 1.5 x ULN
7. Calculated creatinine clearance = 55 mL/min.
8. Age = 18 years.
9. Able and willing to give valid written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Active central nervous system metastases. Definitively treated metastases were allowed if stable for 6 weeks off therapy.
2. Known immunodeficiency or human immunodeficiency virus positivity.
3. Serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would have interfered with the ability of the patient to fulfill the study requirements.
4. Other malignancy, apart from non-melanoma skin cancer, within 3 years prior to the first study drug administration that in the opinion of the investigator had > 10% risk of relapse within 12 months.
5. Significant allergic reaction to prior antibody infusions.
6. Chemotherapy, radiotherapy, or investigational agent within 4 weeks prior to the first study drug administration.
7. Regular corticosteroid, non-steroidal anti-inflammatory drug (other than paracetamol or low-dose aspirin) or other immunosuppressive treatment within 3 weeks prior to the first study drug administration (intermittent dosing permitted if less than 4 doses within a 3-day period).
8. Mental impairment that could have compromised the ability to give informed consent and comply with the requirements of the study.
9. Lack of availability for clinical follow-up assessments.
10. Pregnancy or breastfeeding.
11. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/09/2016
Sample size
Target
Accrual to date
Final
9
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
Ludwig Institute for Cancer Research
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Daiichi Sankyo Co., Ltd.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
Austin Health
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Andrew Scott, MD
Address 0 0
Austin Health, Melbourne, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02252211