AZD8186 First Time In Patient Ascending Dose Study
This is a phase I, open-label, multicentre study of AZD8186 administered orally in patients with advanced castrate-resistant prostate cancer (CRPC), squamous non-small cell lung cancer (sqNSCLC), triple negative breast cancer (TNBC) and known PTEN-deficient/mutated or PIK3CB mutated/amplified advanced solid malignancies as monotherapy and in combination with abiraterone acetate or AZD2014.
Ask AI to explain this studyKey things to know
This describes the study’s primary purpose.
Plus 4 other study approaches.
These are broad labels—not an eligibility decision.
Checked against the public recordLast updated May 29, 2020 · Source: ClinicalTrials.gov
Ask the study team to confirm whether enrollment is open.
Interventional
Locations may change over time.
Study sponsor
What this study is about
- Purpose
- Treatment
- Study type
- Interventional
- Phase
- Phase 1
- Sponsor
- AstraZeneca
- Interventions being studied
- Drug: Part A: AZD8186 monotherapy; Drug: Part B: AZD8186 monotherapy; Drug: Part C1: Abiraterone acetate combination with AZD8186; Drug: Part D1: AZD2014 combination with AZD8186; Drug: Part D2 AZD2014 combination with AZD8186; Drug: Part C2: Abiraterone acetate combination with AZD8186
How this study is categorized
These labels come from structured fields and exact terms in the public record.
Who may be able to participate
The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.
- Provision of signed and dated, written informed consent prior to any study specific procedures
- Male or female, aged 18 years and older
- Histologically or cytologically proven diagnosis of prostate cancer, sqNSCLC, TNBC, or known PTEN-deficient solid malignancy, and is refractory to standard therapies.
- Females should be using adequate contraceptive measures, not be breast feeding and must have negative pregnancy test prior to start of dosing if of child-bearing potential
- WHO/ECOG performance status 0 to 1 with no deterioration over the previous 2 weeks and min life expectancy of 12 weeks
- Tumours that are known to have genomic alterations in PTEN or PIK3CB by local test results may also be eligible. Part B - Tumour amenable to taking of paired biopsies in opinion of the investigator.Patients with TNBC or mCRPC: PTEN-deficient tumours Parts A,B or D1(mCRPC)
- PSA at screening must be ≥2 µg/L.
- Preceding line of treatment included response to anti-androgen, progression documented after withdrawal of the anti-androgen.
- Serum testosterone concentration ≤50 ng/dL sustained by medical or surgical castration Parts A,B or D (TNBC) \- Oestrogen receptor, progesterone receptor and HER2 negative advanced adenocarcinoma of breast. Parts A, B or D1 (solid malignancies) - Consented provision of formalin fixed paraffin embedded blocks/ slides from most recent tissue sample. Part C (all patients):
- May have received treatment with abiraterone acetate, enzalutamide and/or one prior chemotherapy (docetaxel)
- Serum testosterone concentration ≤50 ng/dL sustained by medical or surgical castration.
- Early or confirmed evidence of progressive disease.
- Last PSA value should have increase of ≥ 25% of the first PSA value and an absolute increase of ≥2 ng/mL over the first PSA value
- Serum potassium \> 3.5 mmol/L Parts C2 and D2 \- Prospectively determined eligible PTEN alteration determined by next generation sequencing, protein deficient determined by IHC or PIK3CB mutation/amplification. Part D2 \- Measurable disease (at least 1 lesion ≥10 mm longest diameter or for lymph nodes short axis ≥15 mm) by CT/MRI
- Treatment before study with 1. Nitrosourea or mitomycin C within 6 weeks 2. Investigational agents from previous clinical study within 4 weeks 3. Chemotherapy, immunotherapy or anticancer agents within 4 weeks 4. hormonal therapy
- Treatment before study with 1. Strong inhibitors and strong or moderate inducers of CYP3A4 2. Radiotherapy with a wide field of radiation within 4 weeks,
- With the exception of alopecia or toxicities related to the use of gonadotropin-releasing hormone agonists any unresolved toxicities from prior therapy greater than CTCAE grade 1 at time of study treatment
- Spinal cord compression or brain metastases unless asymptomatic treated and stable and not requiring steroids
- Evidence of severe or uncontrolled systemic diseases including active liver disease (other than malignancy), active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Exclusion crtieria Part C
- Pre-existing Grade 2 or higher chronic diarrhoea
- Major bowel surgery which in the opinion of the Investigator should exclude the patient
- Use of antibiotics to treat chronic infections within 28 days prior to first dose
- Sensitive or narrow therapeutic range substrates of CYP2D6
- Severe or moderate hepatic impairment
- Persistent uncontrolled hypertension (systolic \>160 mmHg/ diastolic \>100 mmHg
Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.
U.S. locations
- Research SiteBoston, Massachusetts
- Research SiteDetroit, Michigan
- Research SiteNew York, New York
- Research SiteSeattle, Washington
- Research SiteMadison, Wisconsin
- Research SiteToronto, Ontario
- Research SiteBarcelona
- Research SiteBarcelona
- Research SitePozuelo de Alarcón
- Research SiteCambridge
- Research SiteLondon
- Research SiteManchester
Source and freshness
Processed from ClinicalTrials.gov. Last public update: May 29, 2020. Always confirm current availability with the study team.