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

NCT03218826 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: NCI-2017-0123218-23710131UM1CA186691
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Advanced Prostate Carcinoma; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Castration-Resistant Prostate Carcinoma; Metastatic Breast Carcinoma; Metastatic Prostate Carcinoma; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm; Advanced Malignant Solid Neoplasm; Anatomic Stage IIIB Breast Cancer AJCC v8; Metastatic Malignant Solid Neoplasm; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Advanced Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicity (DLT)

  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.

  At Day 22

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

  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.

  Up to 3 years

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  At 24 weeks

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

  At 24 weeks

• Maximum Blood Concentrations of Docetaxel When Also Taking AZD8186

  Up to 6 hours after initial treatment

Study Arms (1)

Treatment (docetaxel, PI3Kbeta inhibitor AZD8186)

EXPERIMENTAL

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.

Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: PI3Kbeta Inhibitor AZD8186

Interventions

Docetaxel DRUG

Given IV

Also known as: Docecad, RP 56976, RP-56976, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (docetaxel, PI3Kbeta inhibitor AZD8186)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (docetaxel, PI3Kbeta inhibitor AZD8186)

Pharmacological Study OTHER

Correlative studies

Treatment (docetaxel, PI3Kbeta inhibitor AZD8186)

PI3Kbeta Inhibitor AZD8186 DRUG

Given PO

Also known as: AZD-8186, AZD8186

Treatment (docetaxel, PI3Kbeta inhibitor AZD8186)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• Patients must be able to swallow and retain oral medications and be without gastrointestinal illnesses that would preclude absorption of AZD8186
• Unlimited prior therapies allowed
• Docetaxel appropriate
• Patients who have not received prior docetaxel (or other taxane therapy) in the advanced setting are eligible for all cohorts
• Patients who have previously received docetaxel (or other taxane therapy) in the advanced setting are eligible for the dose escalation cohort only, if anticipated to have maintained taxane sensitivity and in the opinion of the investigator would still benefit from further docetaxel therapy
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Hemoglobin \>= 8 g/L
• Platelets \>= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• PTEN or PIK3CB mutated advanced solid tumor

You may not qualify if:

• HER2 positive breast cancer
• Prior treatment with PI3K/AKT inhibitors
• Any known concurrent RAF or PIK3CA mutation
• Patients who have had chemotherapy, radiotherapy, immunotherapy or anticancer agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of the first dose of study treatment, except hormonal therapy with luteinizing hormone-releasing hormone (LHRH) analogues for medical castration in patients with prostate cancer and breast cancer, which are permitted
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1)
• Patients who are receiving any other investigational agents
• Patients with known, untreated or unstable brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients with treated brain metastases are eligible if the metastases have been radiographically and clinically stable for at least one month; if on steroids for this indication, the patient must be on a stable dose for at least one month
• History of clinically significant allergic reactions attributed to compounds of similar chemical or biologic composition to AZD8186 or docetaxel or to docetaxel itself
• Patients receiving any medications or substances that are strong inhibitors and/or strong or moderate inducers of CYP3A4 are ineligible; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Existing bleeding or condition associated with increased risk of bleeding
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because AZD8186 is a PI3K inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD8186, breastfeeding should be discontinued if the mother is treated with AZD8186; these potential risks may also apply to other agents used in this study
• Human immunodeficiency virus (HIV)-patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have:
• A stable regimen of highly active anti-retroviral therapy (HAART) that does not include strong inhibitors and strong or moderate inducers of CYP3A4
• No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Schram AM, Takebe N, Chen A, Zhou Q, Iasonos A, Silber J, Reynolds M, Hussain S, Gavriliuc M, Smyth LM, Garrison D, Dumbrava EE. A phase I study of AZD8186 in combination with docetaxel in patients with PTEN-mutated or PIK3CB-mutated advanced solid tumors. ESMO Open. 2025 Sep;10(9):105569. doi: 10.1016/j.esmoop.2025.105569. Epub 2025 Sep 11.

  PMID: 40939237 DERIVED

• Schrottmaier WC, Kral-Pointner JB, Salzmann M, Mussbacher M, Schmuckenschlager A, Pirabe A, Brunnthaler L, Kuttke M, Maier B, Heber S, Datler H, Ekici Y, Niederreiter B, Heber U, Blomgren B, Gorki AD, Soderberg-Naucler C, Payrastre B, Gratacap MP, Knapp S, Schabbauer G, Assinger A. Platelet p110beta mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia. Cell Rep. 2022 Nov 8;41(6):111614. doi: 10.1016/j.celrep.2022.111614.

  PMID: 36351402 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Prostatic Neoplasms; Triple Negative Breast Neoplasms

Interventions

Docetaxel; AZD8186

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Grants Administrative Manager
• Organization: Johns Hopkins University/SKCCC

jmurra33@jhmi.edu

4439273568

Study Officials

• Alison M Schram

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2017
• First Posted: July 17, 2017
• Study Start: September 24, 2018
• Primary Completion: July 25, 2022
• Study Completion: October 13, 2025
• Last Updated: April 29, 2026
• Results First Posted: September 21, 2023

Record last verified: 2026-03

Locations

US (8)