Last updated on July 2020

Study of AZD9833 Alone or in Combination With Palbociclib in Women With Advanced Breast Cancer

Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

  • Conditions: ER+ HER2- Advanced Breast Cancer
  • Age: Between 18 - 130 Years
  • Gender: Female

  1. Signed written informed consent.
  2. >= 18 years.
  3. Any menopausal status:
    1. Pre-menopausal women must have commenced treatment with an LHRH agonist at least 4 weeks prior to starting IMP (AZD9833 and/or palbociclib) and must be willing to continue to receive LHRH agonist therapy for the duration of the trial.
    2. Post-menopausal defined according to standard criteria in the protocol.
    3. Histological or cytological confirmation of adenocarcinoma of the breast.
    4. Documented positive oestrogen receptor status of primary or metastatic tumour tissue, according to the local laboratory parameters. HER-2 negative.
    5. Metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit.
    6. Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP.
    7. Prior chemotherapy, endocrine therapy and other therapy in the advanced setting is restricted as follows:
    8. No more than 2 lines of chemotherapy for advanced disease.
    9. Recurrence or progression on at least one line of endocrine therapy in the dvanced/metastatic disease setting.
    10. There is no limit on the number of lines of prior endocrine therapies.
    11. Prior treatment with CDK4/6 inhibitors is permitted.
    12. Women of childbearing potential must agree to use a highly effective contraceptive measure, must not be breast feeding, and must have a negative pregnancy test prior to the start of dosing.
    13. At least one lesion (measurable and/or non-measurable, as per Response Evaluation Criteria in Solid Tumours version 1.1 [RECIST 1.1] that can be accurately assessed at baseline and is suitable for repeated assessment by computed tomography (CT), magnetic resonance imaging (MRI), or plain X-ray; or clinical examination. Blastic-only lesions in bone are not considered assessable.
    14. Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1, with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.

Exclusion criteria

  1. Intervention with any of the following:
  2. Any cytotoxic chemotherapy, investigational agents or other anti-cancer drugs for the treatment of advanced breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of IMP.
  3. Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 (CYP) 3A4/5 sensitive CYP2B6 substrates and drugs which are substrates of CYP2C9 and/or CYP2C19, and which have a narrow therapeutic index ie, warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin or inability to stop use within a suitable washout period prior to receiving the first dose of AZD9833.
  4. Drugs that are known to prolong QT and have a known risk of Torsades de Pointes.
  5. Radiotherapy with a limited field of radiation for palliation within one week of the first dose of IMP, radiotherapy to more than 30% of the bone marrow or a wide field of radiation within 4 weeks of the first dose of IMP.
  6. Major surgical procedure or significant traumatic injury, as judged by the investigator, within 4 weeks of the first dose of IMP, or an anticipated need for major surgery and/or any surgery requiring general anaesthesia during the study.
  7. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting IMP, with the exception of alopecia.
  8. Presence of life-threatening metastatic visceral disease.
  9. Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection* including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV).

*Active viral infection is defined as requiring antiviral therapy. Screening for chronic conditions is not required.

5. Any of the following cardiac criteria:

  1. Mean resting QT interval corrected by Fridericia's formula (QTcF) >470 msec obtained from a triplicate electrocardiogram (ECG).
  2. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (eg, complete left bundle branch block, second- and third-degree heart block), or clinically significant sinus pause. Patients with controlled atrial fibrillation can be enrolled.
  3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as symptomatic heart failure, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome, or unexplained sudden death at <40 years of age. Hypertrophic cardiomyopathy and clinically significant stenotic valve disease.
  4. Left ventricular ejection fraction (LVEF) <50%, and/or experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) Grade 2, cerebrovascular accident, or transient ischaemic attack.
  5. Uncontrolled hypertension. Hypertensive patients may be eligible but blood pressure must be adequately controlled at baseline. Patients may be re-screened regarding the blood pressure requirement.
  6. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  7. Absolute neutrophil count (ANC) <1.5 109/L.
  8. Platelet count <100 109/L.
  9. Haemoglobin <90 g/L.
  10. Alanine aminotransferase (ALT) >2.5 the upper limit of normal (ULN).
  11. Aspartate aminotransferase (AST) >2.5 ULN.
  12. Total bilirubin (TBL) >1.5 ULN or >3 ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia).
  13. Glomerular filtration rate (GFR) <50 mL/min.
  14. Involvement in the planning and conduct of the study (applies to AstraZeneca staff or staff at the study site).
  15. Refractory nausea and vomiting, uncontrolled chronic gastrointestinal (GI) diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9833 and palbociclib.

History of hypersensitivity to active or inactive excipients of AZD9833 or drugs with a similar chemical structure or class to AZD9833.

For subjects in Parts C and D: History of hypersensitivity to active or inactive excipients of palbociclib or drugs with a similar chemical structure or class to palbociclib.

9. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

10. Male subjects are excluded from this study.

Recruitment Status: Open

Brief Description Eligibility Contact Research Team

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