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
Overview
- Phase
- Phase 1
- Intervention
- AZD 1775
- Conditions
- Ovarian Cancer, TNBC, SCLC, Other Solid Tumours
- Sponsor
- AstraZeneca
- Enrollment
- 92
- Locations
- 1
- Primary Endpoint
- Number of treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs) as a measure of safety and tolerability.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open-label, multi-centre, Phase Ib study of AZD1775 designed to assess the safety, tolerability, pharmacokinetics, and anti-tumour activity of AZD1775 monotherapy in patients with advanced solid tumours.
Detailed Description
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Previous chemotherapy for recurrent or metastatic disease.
- •Measurable disease is required for Part B expansion cohorts according to RECIST v1.1 criteria.
- •Radiation therapy completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects.
- •ECOG Performance Status (PS) score of 0-
- •Baseline laboratory values as follows:
- •ANC ≥1500/μL
- •Hgb ≥9 g/dL
- •Platelets ≥100,000/μL
- •ALT and AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases.
- •Serum bilirubin WNL or ≤1.5 x the ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
Exclusion Criteria
- •Any chemotherapy within 3 weeks of the first dose of AZD1775, except hormonal therapy in the refractory cohort.
- •Use of a study drug ≤21 days or 5 half-lives, whichever is shorter.
- •Major surgical procedures ≤28 days, or minor procedures ≤7 days.
- •Grade \>1 toxicity from prior therapy (except alopecia or anorexia).
- •CNS disease other than neurologically stable, treated brain metastases.
- •Prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued two weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug.
- •NYHA ≥ Class
- •Mean resting corrected QT interval (QTc) ≥450 msec for males and ≥470 msec for females.
- •Pregnant or lactating.
- •Serious active infection, or serious underlying medical condition.
Arms & Interventions
AZD1775
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.
Intervention: AZD 1775
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Objective Response Rate (ORR)(Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months.)
- Progression Free Survival (PFS)(Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, project 12 months.)
- PK profile: Plasma concentrations of AZD1775 and PK parameters (Cmax, C8hr, tmax, AUC, tlast, t½λz)(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)
- Disease Control Rate (DCR)(Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months)
- Duration of Response (DoR)(Every 6 weeks until treatment discontinuation as defined by RECIST 1.1, projected 12 months)
- QTc prolongation(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.)