NCT02260661

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

A Phase I, Open-Label, Multicentre, Dose-Escalation Study to Investigate the Safety and Pharmacokinetics of AZD8835 in Patients With Advanced Solid Tumours

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

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.

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 administered as a single agent to patients with advanced solid malignancies. Patients will be treated at a starting dose of 20 mg twice daily (BID), administered weekly on Days 1 and 4 and will be escalated to reach a maximum-tolerated dose (MTD) in patients as defined by dose-limiting toxicities (DLTs). A BID intermittent dosing schedule administered weekly on Days 1 and 4 of an oral formulation of AZD8835 will be used, as deemed optimal and effective in non-clinical studies, primarily to determine the safety and tolerability of AZD8835. The pharmacokinetics (PK) of AZD8835 and potential biological activity will also be investigated. In Part A of this study, AZD8835 will be administered as a single agent in a multiple ascending dose escalation phase to investigate the appropriate monotherapy dose level for clinical use. Additional dosing schedules may be studies, including dosing on Days 1 and 2 of each week, rather than Days 1 and 4. Backfilled pharmacodynamic (PDc) cohorts in selected patients with tumours that have documented mutations in the phosphatidylinositol-4,5- bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene will allow further preliminary assessment of the biological effect of AZD8835 in these patients. Following the single-agent dose-escalation phase of the study, additional patients with tumours that have documented mutations in the PIK3CA gene will be enrolled to a single-agent dose-expansion phase at the MTD or recommended Phase II dose (RP2D) at the selected dose schedule (as appropriate) to explore further the safety, tolerability, PK, and biological activity at the selected dose (Part B). In addition, a further dose-escalation phase will be initiated following the observation of specific pre-determined criteria in the single-agent dose escalation, in which postmenopausal patients with oestrogen receptor positive (ER+), HER2 negative breast cancer will receive AZD8835 in combination with fulvestrant (Part C). The combination dose-escalation phase will investigate the appropriate combination dose level for clinical use. Following the combination dose-escalation phase of the study, additional postmenopausal patients with ER+ breast cancer and tumours with documented mutations of the PIK3CA gene will be enrolled to a AZD8835 and fulvestrant combination dose-expansion phase at the MTD or RP2D (as appropriate) to explore further the safety, tolerability, PK, and biological activity at the selected dose (Part D).

Conditions

• Advanced Solid Malignancies
• Breast Cancer - ER+, HER2 -
• Breast Cancer - ER+, HER2-, PIK3CA Gene Mutation

Interventions

Type	Name	Description
DRUG	AZD8835	AZD8835 is a small molecule that inhibits cancer progression by blocking PI3 kinase pathway components
DRUG	AZD8835	AZD 8835 is a small molecule that inhibits cancer progression by blocking PI3 kinase pathway components
DRUG	AZD8835 in combination with fulvestrant	AZD8835 is a small molecule that inhibits cancer progression by blocking PI3 kinase pathway components. Fulvestrant is approved for the treatment of postmenopausal women with ER+ locally advanced or metastatic breast cancer following progression of disease while receiving anti-estrogen therapy.
DRUG	AZD8835 in combination with fulvestrant	AZD8835 is a small molecule that inhibits cancer progression by blocking PI3 kinase pathway components. Fulvestrant is approved for the treatment of postmenopausal women with ER+ locally advanced or metastatic breast cancer following progression of disease while receiving anti-estrogen therapy

Timeline

• Start date: 2014-11-01
• Primary completion: 2016-07-01
• Completion: 2016-07-01
• First posted: 2014-10-09
• Last updated: 2016-10-10

Locations

9 sites across 2 countries: United States, United Kingdom