Trials / Active Not Recruiting

Active Not RecruitingNCT03218826

PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery

A Phase I Study of AZD8186 in Combination With Docetaxel in Patients With PTEN Mutated or PIK3CB Mutated Advanced Solid Tumors, Potentially Amenable to Docetaxel

Status: Active Not Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 23 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of PI3Kbeta inhibitor AZD8186 when given together with docetaxel in treating patients with solid tumors with PTEN or PIK3CB mutations that have spread to other places in the body (metastatic) or cannot be removed by surgery. PI3Kbeta inhibitor AZD8186 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving PI3Kbeta inhibitor AZD8186 and docetaxel may work better in treating patients with solid tumors.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of PI3Kbeta inhibitor AZD8186 (AZD8186) when administered in combination with docetaxel in patients with PTEN or PIK3CB mutated advanced solid tumors. II. To assess the safety and tolerability of AZD8186 when administered in combination with docetaxel in patients with PTEN or PIK3CB mutated advanced solid tumors. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. Ia. To assess the objective response rate (ORR) of AZD8186 when administered in combination with docetaxel in patients with PTEN or PIK3CB mutated advanced solid tumors. Ib. To assess the clinical benefit rate at 24 weeks of AZD8186 when administered in combination with docetaxel in patients with PTEN or PIK3CB mutated advanced solid tumors. II. To investigate a drug-drug interaction between docetaxel and AZD8186 and correlate drug exposure with pharmacodynamics response. EXPLORATORY OBJECTIVES: I. Examine the pattern of co-mutated genes in PTEN or PIK3CB mutated tumors and their association with treatment response or resistance. II. Describe possible mechanisms of acquired resistance to PI3Kbeta inhibition. III. Evaluation of protein expression of the PTEN gene and its association with treatment response or resistance. IV. Examine isoform-specific AKT inhibition and other downstream target modulation from PI3Kbeta inhibition with AZD8186. OUTLINE: This is a dose-escalation study of PI3Kbeta inhibitor AZD8186. Patients receive docetaxel intravenously (IV) over 1 hour on day 1 and PI3Kbeta inhibitor AZD8186 orally (PO) twice daily (BID) for 5 days each week. Cycles repeat every 21 days until April 30, 2022 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 3 months.

Conditions

Interventions

Type	Name	Description
DRUG	Docetaxel	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	PI3Kbeta Inhibitor AZD8186	Given PO

Timeline

Start date: 2018-09-24
Primary completion: 2022-07-25
Completion: 2026-10-03
First posted: 2017-07-17
Last updated: 2025-10-30
Results posted: 2023-09-21

Locations

8 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03218826. Inclusion in this directory is not an endorsement.