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Advanced Breast CarcinomaPhase 1NCT03218826

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 1 study testing Docetaxel, Laboratory Biomarker Analysis and Pharmacological Study in people with Advanced Breast Carcinoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Docetaxel, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
8 sitesUnited States
Study dates
24 Sep 2018to 13 Oct 2025
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • PTEN loss of function mutation or PIK3CB gain of function mutation identified by local Clinical Laboratory Improvement Act (CLIA) certified next generation sequencing (NGS)
  • Breast cancers patients enrolled on this study must have either:
  • Estrogen receptor positive and HER2 negative breast cancer
  • Triple negative breast cancer
  • Adequate archival tissue (metastatic tissue sample is preferable but primary tumor tissue will be acceptable) or willing to undergo pre-treatment biopsy (for central confirmation of molecular alteration and PTEN immunohistochemical assessment) if adequate archival tissue is unavailable
  • The effects of AZD8186 on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of AZD8186 administration
  • Ability to understand and the willingness to sign a written informed consent document
  • DOSE ESCALATION COHORT: Prior receipt of docetaxel is permitted
  • DOSE ESCALATION COHORT: Measurable disease is not required for enrollment
  • PHARMACODYNAMIC EXPANSION COHORT: Prior receipt of docetaxel is not permitted
  • PHARMACODYNAMIC EXPANSION COHORT: Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • PHARMACODYNAMIC EXPANSION COHORT: Consent to allow mandatory paired (pre- and on- treatment) fresh tissue biopsies if deemed safe to do so for quantitation of Akt pathway signaling proteins
  • DISEASE SPECIFIC EXPANSION COHORTS: Prior receipt of docetaxel is not permitted
  • DISEASE SPECIFIC EXPANSION COHORTS: Patients (excepting the prostate cancer patients) must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with CT scan, MRI, or calipers by clinical exam
  • DISEASE SPECIFIC EXPANSION COHORTS: Breast cancers patients enrolled on this study must have:
  • Metastatic or advanced (incurable and unresectable) HER2 negative breast cancer regardless of estrogen receptor status (both hormone receptor positive and triple negative patients are eligible)
  • Received hormonal therapy, as appropriate based on their hormone receptor status; hormone receptor positive patients who have not received endocrine therapy for recurrent/metastatic disease are eligible, permitted their physician feels they are not appropriate for first line endocrine therapy, for example for high risk visceral metastatic disease
  • DISEASE SPECIFIC EXPANSION COHORTS: Prostate cancers patients enrolled on this study (applies to all prostate cancer patients treated on parts 1, 2, and 3) must have:
  • Metastatic or advanced (incurable and unresectable) castration resistant metastatic cancer
  • Received at least one additional line of anti-androgen therapy with abiraterone or enzalutamide
  • Measurable disease is not required for enrollment

Who cannot join

  • 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
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  • 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
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based test

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • National Cancer Institute Developmental Therapeutics Clinic

    Bethesda, Maryland, 20892

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Docetaxel, Laboratory Biomarker Analysis, Pharmacological Study, PI3Kbeta Inhibitor AZD8186
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis, Prostatic Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DocetaxelDrug

    Also called Docecad, RP 56976, RP-56976, RP56976

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • PI3Kbeta Inhibitor AZD8186Drug

    Also called AZD-8186, AZD8186

    Given PO

Study groups in NCT03218826
Study groupRoleWhat they receive
Treatment (docetaxel, PI3Kbeta inhibitor AZD8186)ExperimentalPatients 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.
Receives: Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: PI3Kbeta Inhibitor AZD8186

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At Day 22

  2. 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.

    Measured: Up to 3 years

Secondary outcomes (3)

  1. Objective Response Rate (ORR)

    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.

    Measured: At 24 weeks

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

    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.

    Measured: At 24 weeks

  3. Maximum Blood Concentrations of Docetaxel When Also Taking AZD8186

    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.

    Measured: Up to 6 hours after initial treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2017
  2. Study start24 Sep 2018
  3. Primary completion25 Jul 2022
  4. Study completion13 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03218826
Sponsor's protocol ID
NCI-2017-01232
Other IDs
NCI-2017-01232, 18-237, 10131, 10131, UM1CA186691
Status last verified
Mar 2026
First submitted
14 Jul 2017
Last updated
29 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 40939237

  • 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.

    PubMed 36351402

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Docetaxel, Laboratory Biomarker Analysis and Pharmacological Study in people with Advanced Breast Carcinoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicity (DLT) (time frame: At Day 22). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03218826, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.

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