Phase I, Dose Study to Look at the Safety and Pharmacokinetics of AZD8835 in Patients With Advanced Solid Tumours

Completed · Phase 1

Conditions studied: Advanced Solid Malignancies, Breast Cancer - ER+, HER2 -, Breast Cancer - ER+, HER2-, PIK3CA Gene Mutation

In brief

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.

Key facts

Study ID

NCT02260661

Run by

AstraZeneca

People needed

20

Starts

2014-11-01

Expected to finish

2016-07-01

Last updated by the study team

2016-10-10

Who can join

Age: 18 and older, up to 130. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• Platelets ≥ 100 x 10\^9, Hb ≥ 90 g/L, ANC ≥ 1.5 x 10\^9/L.
• aPTT ≤ 1.5 x ULN
• Fasting glucose < 140 mg/dL (7.8 mmol/L).
• Glycated haemoglobin (HbA1c) < 8%
• Female patients and male patients with female partners of child bearing potential must be using adequate contraception.

You may not qualify if…

• 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
• Peripheral neuropathy CTCAE v4.03 Grade ≥ 3
• Diarrhoea CTCAE v4.03 Grade ≥ 2
• Acute or chronic pancreatitis
• Clinically manifest diabetes mellitus, history of gestational diabetes mellitus and/or known glucose intolerance.
• Patients currently receiving any medication that has the potential to prolong the QT interval or induce Torsades de Pointes
• Spinal cord compression or brain metastases unless asymptomatic and not requiring steroids for at least 4 weeks
• Patients in the combination arms - known hypersensitivity to fulvestrant
• Therapeutic treatment with Coumadin or any other coumarin-derivative anticoagulant
• Impaired GI function or GI disease that may interfere with absorption of AZD8835 or patients unable to take oral medication
• As judged by the investigator any evidence of severe or uncontrolled systemic disease
• Patients treated with hematopoietic colony-stimulating growth factors e.g., G-CSF, GM-CSF, M-CSF) ≤ 2 weeks prior to start. Erythropoietin or darbepoetin is allowed if it was initiated at least 2 weeks prior to entry

Where it is running

• Research Site — Denver, Colorado, United States
• Research Site — Greenville, South Carolina, United States
• Research Site — Nashville, Tennessee, United States
• Research Site — Houston, Texas, United States
• Research Site — Milwaukee, Wisconsin, United States
• Research Site — Cambridge, United Kingdom
• Sarah Cannon Research Institute, United Kingdom — London, United Kingdom
• Research Site — London, United Kingdom
• Research Site — Manchester, United Kingdom

Full record on ClinicalTrials.gov

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