Safety, Tolerance, PK, and Anti-tumour Activity of AZD1775 Monotherapy in Patients With Advanced Solid Tumours
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase Ib, Open-Label, Multi-Centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumour Activity of AZD1775 Monotherapy in Patients With Advanced Solid Tumours|
- Number of treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs) as a measure of safety and tolerability. [ Time Frame: From first dose of study treatment up to last day of Cycle 1 (21 days) ]The AZD1775 dose is considered safe and tolerable if ≤ 1 of 6 patients experiences a DLT.
- Objective Response Rate (ORR) [ Time Frame: Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months. ]The proportion of patients achieving a complete or partial tumour response (CR or PR) according to RECIST 1.1 criteria.
- Disease Control Rate (DCR) [ Time Frame: Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months ]The proportion of patients achieving a complete response (CR) or partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria
- Duration of Response (DoR) [ Time Frame: Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months ]The time from first documented tumor response until the date of documented progression or death from any cause.
- Progression Free Survival (PFS) [ Time Frame: Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, project 12 months. ]Defined as the time from date of first dose of AZD1775 until the date of objective disease progression or death by any cause as defined by RECIST 1.1.
- PK profile: Plasma concentrations of AZD1775 and PK parameters (Cmax, C8hr, tmax, AUC, tlast, t½λz) [ Time Frame: Pre-dose and 1, 2, 4, 6, 8 and 12 hours post-dose of AZD1775 during Cycle 1-Day 1 and Cycle 1-Day3 or Day-10 of the safety lead-in part of study ]Blood samples will be collected at various timepoints post-dosing
- QTc prolongation [ Time Frame: ECGs collected pre-dose and 1, 2, 4, 6, 8 and 12 hours post-dose in Cycle 1-Day 1 and on Cycle 1-Day 3 or Day 10. ]ECGs will be obtained at various timepoints
|Actual Study Start Date:||July 1, 2015|
|Estimated Study Completion Date:||October 31, 2018|
|Estimated Primary Completion Date:||October 31, 2018 (Final data collection date for primary outcome measure)|
Single-arm study. AZD1775 will be administered for 3 consecutive days at the start of week 1 and week 2 of each 21-day cycle.
This study will be conducted in two parts, designated Part A and Part B. Part A is a safety lead-in. Part B will commence after the safety lead-in and will investigate the safety and efficacy of AZD1775 monotherapy in expansion cohorts of specific tumour types.
Drug: AZD 1775
AZD1775 will be taken orally approximately every 12 hours over 3 days at the start of week 1 and week 2 of each 21-day cycle (Days 1-3 and 8-10), for a total of 12 doses with each treatment cycle.
AZD1775 should be taken approximately 2 hours before or 2 hours after food.
This study is being conducted in two parts, designated Parts A and B. Part A is a safety lead-in consisting of a cohort of approximately 12 patients with advanced solid tumours.
Part B expansion cohorts will investigate AZD1775 monotherapy in advanced tumour types with molecular biomarkers of interest. The tumour types to be evaluated are: 1) ovarian cancer (BRCA1/2 mutation [PARP-failures]), 2) ovarian cancer (BRCA wild-type) with more than three prior lines of treatment, 3) triple negative breast cancer (TNBC), and 4) small-cell lung cancer (SCLC).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02482311
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|Principal Investigator:||Todd M. Bauer, MD||SCRI Development Innovations, LLC|