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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01966445




Registration number
NCT01966445
Ethics application status
Date submitted
17/10/2013
Date registered
21/10/2013
Date last updated
1/07/2019

Titles & IDs
Public title
Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors
Scientific title
A Phase I, First Time in Human, Open-Label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Anti-Her3 Monoclonal Antibody GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors
Secondary ID [1] 0 0
2013-001699-39
Secondary ID [2] 0 0
117158
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - GSK2849330

Experimental: GSK2849330 Part 1 - 1 hour infusion administered intravenously at intervals of one week or more (escalating doses).

Experimental: GSK2849330 Part 2 - Intravenous infusion administered at the dose and schedule established in Part 1


Other interventions: GSK2849330
Solution containing 100 mg/millilter (mL) GSK2849330 for intravenous infusion
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Parts 1 and 2
Timepoint [1] 0 0
Median of 6.143 weeks of drug exposure
Primary outcome [2] 0 0
Number of Participants With Dose-limiting Toxicities (DLTs)-Parts 1 and 2
Timepoint [2] 0 0
Up to 28 days
Primary outcome [3] 0 0
Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Parts 1 and 2
Timepoint [3] 0 0
Baseline and median of 6.143 weeks of drug exposure
Primary outcome [4] 0 0
Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Parts 1 and 2
Timepoint [4] 0 0
Baseline and median of 6.143 weeks of drug exposure
Primary outcome [5] 0 0
Number of Participants With Grade Change From Baseline in Hematology Data-Parts 1 and 2
Timepoint [5] 0 0
Baseline and median of 6.143 weeks of drug exposure
Primary outcome [6] 0 0
Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Parts 1 and 2
Timepoint [6] 0 0
Baseline and median of 6.143 weeks of drug exposure
Primary outcome [7] 0 0
Number of Participants With Change From Baseline in Urinalysis Data With Respect to Normal Range-Parts 1 and 2
Timepoint [7] 0 0
Baseline and median of 6.143 weeks of drug exposure
Primary outcome [8] 0 0
Number of Participants With Change From Baseline in Vital Signs-Parts 1 and 2
Timepoint [8] 0 0
Baseline and median of 6.143 weeks of drug exposure
Primary outcome [9] 0 0
Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Parts 1 and 2
Timepoint [9] 0 0
Median of 6.143 weeks of drug exposure
Secondary outcome [1] 0 0
Maximum Observed Plasma Concentration (Cmax) of GSK2849330-Part 1
Timepoint [1] 0 0
Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose
Secondary outcome [2] 0 0
Cmax of GSK2849330-Part 2
Timepoint [2] 0 0
Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose
Secondary outcome [3] 0 0
Time of Occurrence of Cmax (Tmax) for GSK2849330-Part 1
Timepoint [3] 0 0
Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose
Secondary outcome [4] 0 0
Tmax for GSK2849330-Part 2
Timepoint [4] 0 0
Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose
Secondary outcome [5] 0 0
Area Under the Concentration Time Curve (AUC) to a Fixed Nominal Time (AUC[0 to 168]) and AUC(0 to 336) for GSK2849330-Part 1
Timepoint [5] 0 0
Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose
Secondary outcome [6] 0 0
AUC(0 to 168) and AUC(0 to 336) for GSK2849330-Part 2
Timepoint [6] 0 0
Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose
Secondary outcome [7] 0 0
Serum HER3 From Tumor Tissue-Parts 1 and 2
Timepoint [7] 0 0
Day 1 (pre-dose, 1 hour, 6 hours), Day 2, Day 8, Day 15, Day 29 and follow-up (28 days post last dose)
Secondary outcome [8] 0 0
Overall Response Rate (ORR)-Parts 1 and 2
Timepoint [8] 0 0
Median of 6.143 weeks of drug exposure
Secondary outcome [9] 0 0
Number of Participants With Antibodies to GSK2849330 in Serum
Timepoint [9] 0 0
Median of 6.143 weeks of drug exposure
Secondary outcome [10] 0 0
Percentage of Cluster of Differentiation (CD) Marker
Timepoint [10] 0 0
Median of 6.143 weeks of drug exposure

Eligibility
Key inclusion criteria
- Males and females >=18 years of age (at the time consent is obtained).

- Written informed consent provided.

- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group
(ECOG) scale.

- Sufficient archival tumor specimen is available for HER3 immunohistochemistry (IHC)
analysis, or subject is willing to undergo a fresh tumor biopsy for HER3 IHC analysis.

- Histologically or cytologically confirmed diagnosis of one of the following solid
tumor malignancies for which no standard therapeutic alternatives exist: bladder
cancer, breast cancer, castrate-resistant prostate cancer, cervical cancer, colorectal
cancer (CRC), gastric cancer, hepatocellular carcinoma (HCC), melanoma, non-small cell
lung cancer (NSCLC), ovarian cancer, pancreatic cancer, squamous cancers of the head
and neck region (including parotid and nasopharynx).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects with leptomeningeal or brain metastases or spinal cord compression.

- Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).

- Concurrent medical condition that would jeopardize compliance.

- Receiving chronic immunosuppressive therapies (includes daily steroid doses in excess
of 20 milligrams [mg]/day of prednisone).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
Single group
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
26/11/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/09/2017
Sample size
Target
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [2] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [3] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Utah
Country [4] 0 0
Netherlands
State/province [4] 0 0
Amsterdam
Country [5] 0 0
Netherlands
State/province [5] 0 0
Groningen
Country [6] 0 0
Netherlands
State/province [6] 0 0
Nijmegen
Country [7] 0 0
Netherlands
State/province [7] 0 0
Rotterdam

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Human Epidermal Growth Factor Receptor 3 (HER3) expression is seen across a wide variety of
solid malignancies and is associated with poor prognosis. Up-regulation of HER3 expression
and activity is also associated with resistance to multiple pathway inhibitors. GSK2849330, a
monoclonal antibody targeting HER3, is a new agent for subjects whose tumors express HER3.
This study is a phase I, first time in human, open-label, dose escalation study. The purpose
of this study is to investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD)
of GSK2849330 in subjects with advanced HER3-positive solid tumors. The study will be
conducted in two parts. Part 1 (Dose-Escalation Phase) will include dose escalation and PK/PD
cohorts to evaluate safety, PK, and PD to guide selection of dose regimen(s) for Part 2. In
Part 2 (Expansion Cohorts), up to 3 cohorts will be enrolled at the dose regimen(s) selected
based on Part 1 data, to evaluate safety in a larger cohort of subjects at the recommended
dose regimen and also to evaluate preliminary evidence of clinical benefit.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01966445
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
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