Phase I, Dose Study to Look at the Safety and Pharmacokinetics of AZD8835 in Patients With Advanc… (NCT02260661) | Clinical Trial Compass
CompletedPhase 1
Phase I, Dose Study to Look at the Safety and Pharmacokinetics of AZD8835 in Patients With Advanced Solid Tumours
United States20 participantsStarted 2014-11
Plain-language summary
First time in patients study of AZD8835. The study has four parts. Part A AZD8835 is administered as a single agent in a multiple ascending dose escalation phase to investigate dose level for monotherapy. Part B follows the multiple ascending dose phase, additional patients with tumors with documented PIK3CA gene mutation will be enrolled to a single dose expansion phase. Part C is a second dose escalation phase in which post-menopausal patients with estrogen receptor positive (ER+), HER2 negative breast cancer will receive AZD8835 in combination with fulvestrant. Part D follows the combination dose escalation phase of the study, additional postmenopausal patients with ER+/HER2 negative breast cancer with documented PIK3CA gene mutation will be enrolled to a AZD8835 and fulvestrant combination dose-expansion phase at maximum tolerated dose or recommended phase II dose.
Who can participate
Age range18 Years – 130 Years
SexALL
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Inclusion criteria
✓. Part A: Histological or cytological confirmation of a solid tumor and disease progression. Part B: Histological or cytological confirmation of ER positive, HER2 negative breast cancer and disease progression or any other solid tumor with a PIK3CA gene mutation. Part C: Histological or cytological confirmation of ER positive, HER2 negative postmenopausal breast cancer with locally advanced or metastatic disease that is eligible for fulvestrant treatment. Part D: Histological or cytological confirmation of ER positive, HER2 negative postmenopausal breast cancer with locally advanced or metastatic disease that is eligible for fulvestrant treatment. Patients must also present with a tumor related mutation of the PIK3CA gene.
✓. Availability of archival tumour tissue sample. If archival sample is not available, a fresh tumour biopsy must be provided.
✓. At least one measurable lesion per RECIST v1.1. However, breast cancer patients with only bone disease are also eligible.
✓. ECOG Performance Status 0-1.
✓. Adequate organ function at baseline:
✓. Serum total bilirubin ≤ 1.5 x ULN and AST/SGOT and ALT/SGPT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present.
✓. Creatinine ≤ 1.5 x ULN, or calculated or measured creatinine clearance ≥ 50 mL/min, or 24-hour measured urine creatinine clearance ≥ 50 mL/min.
What they're measuring
1
Determine the maximum tolerated dose (MTD) or recommended Phase II dose of oral AZD8835 as a single agent and in combination with fulvestrant
Timeframe: At the end of one cycle of treatment
2
Establish the preliminary safety and tolerability profile of oral AZD8835 as a single agent and in combination with fulvestrant
✓. Platelets ≥ 100 x 10\^9, Hb ≥ 90 g/L, ANC ≥ 1.5 x 10\^9/L.
Exclusion criteria
✕. Recent chemotherapy, radiotherapy, hormonal therapy, immunotherapy or investigational drugs within 21 days or 5 half-days from enrolment.
✕. Received palliative/focal radiotherapy within 2 weeks of first dose of study treatment.
✕. Major surgery ≤ 21 days from beginning of study drug
✕. Any of the following cardiac criteria: CHF \> Class II, cardiac ventricular arrhythmia requiring therapy, unstable angina or new-onset angina, QTcF interval \>470ms, abnormal ECHO or MUGA at baseline (LVEF \<50%).
✕. Leptomeningeal disease
✕. Part A: Intolerable AEs due to other PI3K inhibitors, dual PI3K and mTOR inhibitors or AKT inhibitors. Parts B, C, and D: Prior exposure to any of the following: pharmacological inhibitors of AKT, PI3K, or dual PI3K and mTOR kinase activity
✕. Strong inhibitors and potent inducers of CYP3A4