Status:
COMPLETED
Phase I, Dose Study to Look at the Safety and Pharmacokinetics of AZD8835 in Patients With Advanced Solid Tumours
Lead Sponsor:
AstraZeneca
Conditions:
Advanced Solid Malignancies
Breast Cancer - ER+, HER2 -
Eligibility:
All Genders
18-130 years
Phase:
PHASE1
Brief 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 monother...
Detailed Description
AZD8835 is a novel small molecule that inhibits cancer progression by blocking PI3 kinase pathway components p110α and p110δ. In this first-time-in-patient study, AZD8835 will initially be administer...
Eligibility Criteria
Inclusion
- 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.
Exclusion
- 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
Key Trial Info
Start Date :
November 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 1 2016
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT02260661
Start Date
November 1 2014
End Date
July 1 2016
Last Update
October 10 2016
Active Locations (9)
Enter a location and click search to find clinical trials sorted by distance.
1
Research Site
Denver, Colorado, United States
2
Research Site
Greenville, South Carolina, United States
3
Research Site
Nashville, Tennessee, United States
4
Research Site
Houston, Texas, United States