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Genital Diseases, Male

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Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Tubulin Modulators

Antimitotic Agents

Patients receive docetaxel IV over 1 hour on day 1 and PI3Kbeta inhibitor AZD8186 PO BID for 5 days each week. Cycles repeat every 21 days until April 30, 2022 in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Pharmacological Study

PI3Kbeta Inhibitor AZD8186

Alison M Schram

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.

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.

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

The number of DLTs at each dose level will determine the MTD or RP2D of PI3Kbeta inhibitor AZD8186 when administered in combination with docetaxel in patients with PTEN or PIK3CB mutated advanced solid tumors.

Patient safety and tolerability will be described according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version for routine toxicity reporting and CTCAE, version 5 for serious adverse events only.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by imaging: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. For participants with prostate cancer who do not have sites of disease on imaging, objective response is the reduction of prostate specific antigen (PSA) level of 50% or more.

Will be assessed by modified Response Evaluation Criteria in Solid Tumors version 1.1. Will assess the CBR of PI3Kbeta inhibitor AZD8186 when administered in combination with docetaxel in patients with PTEN or PIK3CB mutated advanced solid tumors. A 90% confidence interval on CBR will be calculated assuming binomial proportions.

Will investigate the concentration of docetaxel in the blood when participants also take the PI3Kbeta inhibitor AZD8186. Blood is drawn after docetaxel infusion and before the participant takes AZD8186, after the participant takes AZD8186, and again 6 hours after taking AZD8186. Blood concentrations of docetaxel are measured at each collection time. The change in concentrations at the different dose levels may suggest whether AZD8186 impacts how much docetaxel is still in the blood over time.

National Cancer Institute (NCI)

Patients receive docetaxel 75 mg/m\^2 IV over 1 hour on day 1 and PI3Kbeta inhibitor AZD8186 60 mg PO BID for 5 days each week. Cycles repeat every 21 days until April 30, 2022 in the absence of disease progression or unacceptable toxicity.

Dose Level 1

Patients receive docetaxel 75 mg/m\^2 IV over 1 hour on day 1 and PI3Kbeta inhibitor AZD8186 30 mg PO BID for 5 days each week. Cycles repeat every 21 days until April 30, 2022 in the absence of disease progression or unacceptable toxicity.

Dose Level -1

Patients receive docetaxel 60 mg/m\^2 IV over 1 hour on day 1 and PI3Kbeta inhibitor AZD8186 60 mg PO BID for 5 days each week. Cycles repeat every 21 days until April 30, 2022 in the absence of disease progression or unacceptable toxicity.

Dose Level -1B

Dose Level 1 With Growth Factors

Patients receive docetaxel 75 mg/m\^2 IV over 1 hour on day 1 and PI3Kbeta inhibitor AZD8186 120 mg PO BID for 5 days each week. Cycles repeat every 21 days until April 30, 2022 in the absence of disease progression or unacceptable toxicity.

Dose Level 2

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Height

Weight

Body Surface Area

Grants Administrative Manager

Number of Participants With Dose Limiting Toxicity (DLT)

Number of Participants With Adverse Events (AEs) Grades 3-5

Objective Response Rate (ORR)

Clinical Benefit Rate (CBR) Defined as Complete Response (CR), Partial Response (PR), or Stable Disease

Spots Global Cancer Trial Database for pi3kbeta inhibitor azd8186