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Solid TumorPhase 1/2NCT04001569

AZD8186 and Paclitaxel in Advanced Gastric Cancer

A Phase 1/2 study testing AZD8186 in combination with paclitaxel in people with Solid Tumor and Stomach Cancer, run by Seoul National University Bundang Hospital at 3 sites in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

AZD8186 is an orally-dosed, selective Phosphatidylinositol 3-kinase (PI3K) β/δ inhibitor that binds to PI3Kβ and PI3Kδ, and inhibits kinase activity and downstream pathways in vitro and in vivo. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Solid Tumor, Stomach Cancer
What is being tested?
AZD8186 in combination with paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
3 sitesSouth Korea
Study dates
14 May 2019to 31 Dec 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

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

Who may be able to join

  • Have the willingness to sign a written informed consent document prior to any study specific procedures
  • Age ≥ 19 years of male and female
  • At each phase of the trial, subjects who meet the following requirements in the appropriate phase will be enrolled.
  • Phase 1b: Subjects with a histologically confirmed metastatic solid tumor that have progressed after treatment with approved therapies or for which there is no standard effective therapy available.
  • Phase 2b: Subjects with histologically confirmed locally advanced or metastatic gastric cancer that have progressed after treatment with first-line fluoropyrimidine-based chemotherapy, with PTEN loss by immunohistochemistry (IHC), PTEN gene abnormality (PTEN gene deletion or loss of function mutation) or Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta(PIK3CB) gene abnormality (amplification or gain of function mutation) identified by next generation sequencing (NGS). If the subject received adjuvant chemotherapy after curative gastric resection and lymph node dissection, adjuvant chemotherapy is considered to be the first-line palliative chemotherapy if the disease recurred during adjuvant chemotherapy or within 6 months after the completion of adjuvant chemotherapy.
  • Patients must have measurable disease based on RECIST 1.1 (Phase 2 part only). Measurable disease will not be required for enrollment in the phase1b part. Patients with evaluable lesion only (without measurable lesion) can be enrolled in the phase 1b part.
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  • Eastern Cooperative Oncology Group(ECOG) performance status 0-1
  • Patients must have adequate organ and marrow function as defined below:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, B. Hemoglobin ≥ 9.0 g/dL, C. Platelet ≥ 100 x 109/L, D. Aspartate transaminase(AST) and/or alanine transaminase(ALT) ≤ 3 × upper limit of normal (ULN) [Regardless of the presence of liver metastases, only subjects who have AST/ALT ≤ 3 × ULN can be enrolled in phase 1b part; In phase 2 part, subjects with AST and/or ALT ≤ 5 X ULN can be enrolled if they have liver metastases] E. Total bilirubin: ≤ 1 × ULN; Subjects with a bile duct obstruction will be eligible if they meet the criteria after appropriate bile drainage; Patients with Gilbert syndrome should also be registered after confirming that the total bilirubin level is within the normal range through a follow-up screening test F. Serum creatinine clearance >50 milliliter/min
  • Adequate cardiac function with corrected QT interval(QTc) < 470 msec
  • Patients must be able to swallow and retain oral medications
  • Serum β-human chorionic gonadotropin (HCG) test negative within 14 days before the first administration (women of childbearing potential only).
  • Requirements for contraception must be followed.

Who cannot join

  • Active central nervous system (CNS) lesions (ie, those with radiologically unstable or symptomatic brain lesions). For those who receive radiation or surgical treatment, the subject can be enrolled if the subject is maintained without evidence of CNS disease progression for more than 4 weeks. However, patients with a leptomeningeal metastases are excluded.
  • Treatment with any of the following:
  • Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
  • Any cytotoxic chemotherapy from a previous treatment regimen within 14 days. If the subject received an investigational drug from another clinical trial, the subject can be enrolled after 2 weeks of last administration and more than 5 x half-life of the investigational drug. If monoclonal antibody therapy was given, the subject can be enrolled after four weeks after the last dose.
  • Strong or moderate inducers or inhibitors of CYP3A4 within 2 weeks before the first dose of study treatment
  • Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
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  • Any previous exposure to a Phosphatidylinositol 3-kinase (PI3K) inhibitor (including selective or pan PI3K inhibitors), Akt, mammilian target of rapamycin (mTOR) inhibitors.
  • History of allogeneic bone marrow transplantation or organ transplantation
  • History of another primary cancer (excluding gastric cancer):
  • Exceptions are:
  • Adequately treated non-melanoma skin cancer (basal cell or squamous cell carcinoma), curatively treated in situ cancer of the cervix, completely resected thyroid cancer without distant metastasis in which all treatment has been completed (Appropriate wound healing is required prior to clinical trial enrollment)
  • Other curatively treated solid tumors except for gastric cancer with no evidence of disease recurrence at least 36 months before participating in this trial
  • Clinically significant cardiovascular disease including but not limited to:
  • Acute coronary syndrome within the 6 months prior to the initiation of study drug (including myocardial infarction or unstable angina, Coronary Artery Bypass Graft surgery, percutaneous coronary intervention and stenting)
  • Current heart failure or past history of heart failure
  • Current or past history of clinically significant cardiac arrhythmia (eg, complete left bundle branch block, third degree heart block)
  • Any risk factors that prolong QTc or increase the probability of arrhythmia, including medication (eg: heart failure, hypokalemia, congenital long QT syndrome, history of Torsades de Pointes)
  • Persistent uncontrolled hypertension as defined by: systolic >180 mmHg or diastolic >100 mmHg despite medical treatment
  • Seropositivity of HIV, or known active hepatitis B and/or active hepatitis C infection. Hepatitis B carriers may be enrolled if prophylactic use of an antiviral agent with minimal interaction with CYP3A4 is administered to inhibit hepatitis B virus (HBV) activation (eg. Entecavir, adefovir)
  • Impairment of gastrointestinal function or gastrointestinal disorders (eg. untreated ulcerative disorders; uncontrolled nausea, vomiting, or diarrhea; absorption disorder syndrome; small bowel resection; ileostomy). Patients with ileostomy will not allowed to be enrolled, but patients with colostomy can be enrolled to this study.
  • As judged by the Investigator, all other symptoms and associated disease for which the investigator determined that participation in this study is contraindicated (e.g. Infection/inflammation; severe liver dysfunction; bilateral diffuse interstitial lung disease; uncontrolled renal disease; unstable heart and lung disease; hemorrhagic disease; intestinal obstruction; unable to swallow oral pills; social and psychological problems, etc)
  • Pregnant or lactating women.
  • Medical, psychiatric, cognitive, or other conditions that may interfere with the ability of the subject to understand the study information, provide the informed consent, follow the protocol process, or complete the clinical trial
  • Hypersensitivity to paclitaxel

Trial locations and contacts

3 sites in 1 country.

Yong Min Shin contact

82-31-787-8324

r0012@snubh.org

Keun-Wook Lee, MD. & Ph.D contact

82-31-787-7039

hmodoctor@snubh.org

South Korea3 sites, 3 recruiting

  • Hallym University Sacred Heart Hospital

    Anyang-si, Gyeonggi-do, 14068

    Dae Young Zhang, MD. & Ph.D., fhdzang@hallym.ac.kr

    Not yet recruiting

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 13620

    Keun-Wook Lee, MD. & Ph.D, 82-31-787-7039, hmodoctor@snubh.org

    Recruiting

  • Asan Medical Center

    Seoul, 05505

    Min-Hee Ryu, MD. & Ph.D., miniryu@amc.seoul.kr

    Not yet recruiting

Other trials in South Korea

About this study

Official title: Phase1b/2 Study of AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer

AZD8186 is an orally-dosed, selective Phosphatidylinositol 3-kinase (PI3K) β/δ inhibitor that binds to PI3Kβ and PI3Kδ, and inhibits kinase activity and downstream pathways in vitro and in vivo. AZD8186 has shown significant anti-tumor activity in PTEN-deficient preclinical models, including prostate, triple negative breast cancer, squamous lung and germinal center diffuse large B-cell lymphoma models. PTEN deficiency is reported in approximately 20% of patients with gastric cancer and in 35-48% of those with human epidermal growth factor receptor 2(HER2)-positive gastric cancer. To date, there have been no clinical trials with AZD8186 alone or in combination with paclitaxel in advanced gastric cancer. Therefore, it is very important to conduct clinical trials of combination therapy of AZD8186 and paclitaxel in patients with metastatic/recurrent gastric cancer who have failed previous therapy, and to identify the clinical factors and biomarkers that predict effects of the combination therapy.

The purpose of the study is to define the maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D) of paclitaxel and AZD8186 combination therapy in patients with advanced tumors and to evaluate the efficacy of paclitaxel and AZD8186 combination therapy as a second-line therapy in patients with advanced gastric cancer with PTEN aberrations. This study is divided into Phase 1b and Phase 2.

Being tested
AZD8186 in combination with paclitaxel
Medical subject headings
Stomach Neoplasms

What participants receive

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

  • AZD8186 in combination with paclitaxelDrug

    Phase 1b is planned for a 4-stage dose level and the traditional 3+3 design is applied. The RP2D will be determined based on the MTD and toxicity profiles.

    In phase 2 part, RP2D from the phase 1b part will be applied.

    • AZD8186 ( )mg po bid, 5 days on, 2 days off
    • Paclitaxel ( )mg/m² on D1,8,15 every 4 weeks
Study groups in NCT04001569
Study groupRoleWhat they receive
AZD8186 in combination with paclitaxelExperimentalNot described
Receives: Drug: AZD8186 in combination with paclitaxel

What is being measured

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

  1. Maximal tolerated dose

    Measured: 4 weeks

  2. Recommended phase 2 dose

    Measured: 4 weeks

  3. Progression-free survival rate

    Measured: 4 months

Secondary outcomes (5)

  1. Dose-limiting toxicity

    Dose-limiting toxicity (DLT) assessment will be performed during the first cycle in phase 1b part, and is based on NCI-CTCAE (version 4.0).

    Measured: 4 weeks

  2. Overall survival

    Measured: 1-year

  3. Progression-free survival

    Measured: 1-year

  4. Objective response rate

    Measured: 1-year

  5. Adverse event

    Measured: 1-year

Timeline

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

  1. First posted28 Jun 2019
  2. Study start14 May 2019
  3. Primary completion31 Dec 2021 (estimated)
  4. Study completion31 Dec 2022 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04001569
Sponsor's protocol ID
KCSG-ST18-20
Status last verified
Jun 2019
First submitted
23 Jun 2019
Last updated
28 Jun 2019
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Suh KJ, Ryu MH, Zang DY, Bae WK, Lee HS, Oh HJ, Kang M, Kim JW, Kim BJ, Mortimer PGS, Kim HJ, Lee KW. AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20). Oncologist. 2023 Sep 7;28(9):e823-e834. doi: 10.1093/oncolo/oyad059.

    PubMed 37036671

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AZD8186 in combination with paclitaxel in people with Solid Tumor and Stomach Cancer, run by Seoul National University Bundang Hospital at 3 sites in South Korea.

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 13 inclusion and 24 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: status not confirmed, as of the sponsor's last update on 28 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in South Korea. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Yong Min Shin (82-31-787-8324, r0012@snubh.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximal tolerated dose (time frame: 4 weeks). The study lists 3 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 NCT04001569, which also lists 1 linked publication.

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 28 Jun 2019.

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