Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03616587
Recruitment Status : Recruiting
First Posted : August 6, 2018
Last Update Posted : February 27, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE July 6, 2018
First Posted Date  ICMJE August 6, 2018
Last Update Posted Date February 27, 2019
Actual Study Start Date  ICMJE October 11, 2018
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2018)
  • The number of subjects with dose-limiting toxicity, as defined in the protocol. [ Time Frame: Minimum observation period 28 days on treatment. ]
    Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria.
  • The number of subjects with treatment-related adverse events as assessed by CTCAE v4.03. [ Time Frame: Minimum observation period 28 days on treatment, and will continue until the subject is off the study (approximately 1 year). ]
    Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of subjects with treatment-related adverse events assessed by CTCAE v4.03.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03616587 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2018)
  • Objective Response Rate [ Time Frame: Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year). ]
    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
  • Duration of Response [ Time Frame: Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year). ]
    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
  • Clinical benefit rate at 24 weeks [ Time Frame: Up to 24 weeks ]
    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
  • Percentage Change in Tumour Size [ Time Frame: Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year). ]
    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
  • Progression Free Survival [ Time Frame: Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year). ]
    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
  • Maximum Observed Plasma Concentration (Cmax) of AZD9833 alone or in combination with Palbociclib [ Time Frame: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks ) ]
    Blood samples will be collected to assess plasma concentrations of AZD9833 alone or in combination with Palbociclib at a series of timepoints to derive Cmax
  • Time to observed Cmax (Tmax) for AZD9833 alone or in combination with Palbociclib [ Time Frame: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks ) ]
    Blood samples will be collected to assess plasma concentrations of AZD9833 alone or in combination with Palbociclib at a series of timepoints to derive Tmax
  • Area under the plasma concentration-time curve (AUC) for AZD9833 alone or in combination with Palbociclib [ Time Frame: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks ) ]
    Blood samples will be collected to assess plasma concentrations of AZD9833 alone or in combination with Palbociclib at a series of timepoints to derive AUC
  • Renal clearance (CLR) for AZD9833 [ Time Frame: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks ) ]
    Urine samples will be collected to assess urine concentrations of AZD9833 at a series of timepoints to derive renal clearance
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of AZD9833 Alone or in Combination With Palbociclib in Women With Advanced Breast Cancer
Official Title  ICMJE A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination With Palbociclib in Women With ER Positive, HER2 Negative Advanced Breast Cancer
Brief Summary A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination with Palbociclib in Women with ER Positive, HER2 Negative Advanced Breast Cancer
Detailed Description This is a first-in-human study of AZD9833 monotherapy (Parts A and B) and AZD9833 in combination with palbociclib (Parts C and D) in women with ER Positive HER2 Negative advanced breast cancer that is not amenable to treatment with curative intent. Parts A and C of the study allow for an escalation of AZD9833 dose alone (Part A) or in combination with palbociclib (Part C). In Parts B and D of the study, eligible subjects will be randomised to receive selected doses of AZD9833 alone (Part B) or in combination with palbociclib (Part D).
Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

This is a first-in-human study of AZD9833 monotherapy (Parts A and B) and AZD9833 in combination with palbociclib (Parts C and D) in women with ER Positive HER2 Negative advanced breast cancer that is not amenable to treatment with curative intent. Parts A and C of the study allow for an escalation of AZD9833 dose alone (Part A) or in combination with palbociclib (Part C). In Parts B and D of the study, eligible subjects will be randomised to receive selected doses of AZD9833 alone (Part B) or in combination with palbociclib (Part D).

This study will include up to 240 evaluable subjects, divided among the four study parts as follows:

  • Part A: Up to 96 subjects (up to eight cohorts of up to 12 subjects)
  • Part B: Up to 48 subjects (four cohorts with up to 12 subjects)
  • Part C: Up to 48 subjects (up to four cohorts of up to 12 subjects)
  • Part D: Up to 48 subjects (depending on the results observed in Part B)
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE ER+ HER2- Advanced Breast Cancer
Intervention  ICMJE
  • Drug: AZD9833
    Part A: AZD9833 monotherapy dose escalation.
  • Drug: AZD9833 with palbociclib
    Part C: AZD9833 in combination with palbociclib dose escalation.
  • Drug: AZD9833
    Part B: AZD9833 monotherapy expansion
  • Drug: AZD9833 with palbociclib
    Part D: AZD9833 in combination with palbociclib expansion
Study Arms
  • Experimental: AZD9833 monotherapy dose escalation
    Intervention: Drug: AZD9833
  • Experimental: AZD9833 monotherapy dose expansion
    Intervention: Drug: AZD9833
  • Experimental: AZD9833 with palbociclib dose escalation
    Intervention: Drug: AZD9833 with palbociclib
  • Experimental: AZD9833 with palbociclib dose expansion
    Intervention: Drug: AZD9833 with palbociclib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 2, 2018)
165
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2018)
240
Estimated Study Completion Date November 30, 2021
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  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.
  4. Histological and cytological confirmation of adenocarcinoma of the breast.
  5. Documented positive oestrogen receptor status of primary or metastatic tumour tissue, according to the local laboratory parameters. HER-2 negative.
  6. Metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit.
  7. Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP.
  8. Prior chemotherapy, endocrine therapy and other therapy in the advanced setting is restricted as follows:

    1. No more than 2 lines of chemotherapy for advanced disease.
    2. Recurrence or progression on at least one line of endocrine therapy in the dvanced/metastatic disease setting.
    3. There is no limit on the number of lines of prior endocrine therapies.
    4. Prior treatment with CDK4/6 inhibitors is permitted.
  9. 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.
  10. 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.
  11. 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:

    1. 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.
    2. Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 3A4/5 (CYP3A4/5) and sensitive cytochrome P450 2B6 (CYP2B6) substrates or inability to stop use within a suitable washout period prior to receiving the first dose of AZD9833.
    3. Drugs that are known to prolong QT and have a known risk of Torsades de Pointes.
    4. 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.
    5. 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 during the study.
  2. 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.
  3. Presence of life-threatening metastatic visceral disease.
  4. 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. 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:

    1. Absolute neutrophil count (ANC) <1.5 × 109/L.
    2. Platelet count <100 × 109/L.
    3. Haemoglobin <90 g/L.
    4. Alanine aminotransferase (ALT) >2.5 × the upper limit of normal (ULN).
    5. Aspartate aminotransferase (AST) >2.5 × ULN.
    6. Total bilirubin (TBL) >1.5 × ULN or >3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia).
    7. Glomerular filtration rate (GFR) <50 mL/min.
  7. Involvement in the planning and conduct of the study (applies to AstraZeneca staff or staff at the study site).
  8. 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.

Sex/Gender
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Pre-menopausal or Post-menopausal women
Ages 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: Cancer Study Locator 877 400 4656 AstraZeneca@emergingmed.com
Listed Location Countries  ICMJE Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03616587
Other Study ID Numbers  ICMJE D8530C00001
2018-000667-92 ( EudraCT Number )
138396 ( Registry Identifier: IND )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Richard Baird, MD PhD FRCP Breast Cancer Research Unit, University of Cambridge
Study Director: Justin Lindemann, MBChB MBA AstraZeneca
PRS Account AstraZeneca
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP