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Open Label Prostate Cancer Study

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01162395
Recruitment Status : Completed
First Posted : July 14, 2010
Last Update Posted : January 12, 2016
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE July 13, 2010
First Posted Date  ICMJE July 14, 2010
Last Update Posted Date January 12, 2016
Study Start Date  ICMJE August 2010
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2012)
To investigate the safety and tolerability of AZD3514 when given orally to patients with CRPC. [ Time Frame: At every visit. ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2010)
To investigate the safety and tolerability of AZD3514 when given orally to patients with castration resistant prostate cancer (CPRC) [ Time Frame: At every visit. ]
Change History Complete list of historical versions of study NCT01162395 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2012)
  • To define the MTD, if possible, a lower biologically-effective dose(s) or maximum feasible dose (if decided by the Safety Review Committee (SRC) and AstraZeneca). [ Time Frame: After each Cohort. ]
  • To characterise the PK of AZD3514 after a single oral dose and at steady state after multiple oral doses. [ Time Frame: After each Cohort. ]
  • To obtain an assessment of the activity of AZD3514 as monotherapy and/or in combination with abiraterone acetate on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Visits 1, 4, 6, 7, 9, 10, follow-up visits, discontinuation visit ]
  • To obtain a preliminary assessment of the anti-tumour activity of AZD3514 as monotherapy and/or in combination with abiraterone acetate by evaluation of counts of Circulating Tumour Cells (CTCs). [ Time Frame: Visits 1, 6, 8, 9, 10, follow-up visits, discontinuation visit ]
  • To obtain an assessment of the activity of AZD3514 as monotherapy and/or in combination with abiraterone acetate on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Visits 1, 10, follow-up visits, discontinuation visit ]
  • To investigate safety, tolerability, MTD (and/or biologically-effective dose(s) or maximum feasible dose) and PK of AZD3514 and abiraterone when administered in combination, in patients who have not received prior treatment with abiraterone acetate [ Time Frame: At every visit ]
  • To compare the PK of AZD3514 monotherapy in patients who have been fed or fasted before the administration of study treatment [ Time Frame: At visits 2 and 4 ]
  • To investigate the effect of AZD3514 on biomarkers of AR expression in paired pre- and post-dose tumour biopsies. [ Time Frame: July 2012 - Feb 2013 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2010)
  • To define the maximum tolerated dose, if possible, a lower biologically-effective dose(s) or maximum feasible dose of AZD3514. [ Time Frame: After each Cohort. ]
  • To characterise the pharmacokinetics of AZD3514 after a single oral dose and at steady state after multiple oral doses. [ Time Frame: After each Cohort. ]
  • To obtain an assessment of the activity of AZD3514 on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Visit 1, 4, 6, 7, 9, 10, Follow up visits and Discontinuation visit. ]
  • To obtain an assessment of the activity of AZD3514 on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Visit 4 ]
  • To obtain an assessment of the activity of AZD3514 on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Visit 6 ]
  • To obtain an assessment of the activity of AZD3514 on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Visit 7 ]
  • To obtain an assessment of the activity of AZD3514 on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Visit 9 ]
  • To obtain an assessment of the activity of AZD3514 on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Visit 10 ]
  • To obtain an assessment of the activity of AZD3514 on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Follow up visits ]
  • To obtain an assessment of the activity of AZD3514 on the circulating levels of prostate-specific antigen (PSA). [ Time Frame: Discontinuation visit. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open Label Prostate Cancer Study
Official Title  ICMJE A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD3514 in Patients With Metastatic Castration-Resistant Prostate Cancer.
Brief Summary The main purpose of the study is to investigate the safety and tolerability of AZD3514 when given orally to patients with castration-resistant prostate cancer (CRPC)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE Drug: AZD3514
Patients will be given AZD3514 orally as a single dose, and then multiple once daily dosing following a 5-9 day washout.
Study Arms  ICMJE Experimental: A
Ascending doses of AZD3514 administered orally to patients to define the maximum tolerated dose (MTD)
Intervention: Drug: AZD3514
Publications * James GD, Symeonides SN, Marshall J, Young J, Clack G. Continual reassessment method for dose escalation clinical trials in oncology: a comparison of prior skeleton approaches using AZD3514 data. BMC Cancer. 2016 Aug 31;16:703. doi: 10.1186/s12885-016-2702-6.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: March 27, 2014)
64
Original Estimated Enrollment  ICMJE
 (submitted: July 13, 2010)
50
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males aged 20 years or older.
  • Histologically or Cytologically proven diagnosis of prostate cancer for which no standard therapy is currently considered appropriate.
  • Documented evidence of metastatic prostate cancer
  • Presence of progressive disease defined as one or more:
  • Biochemical progression of the prostate cancer
  • Progression as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 guidelines
  • Two or more new metastatic bone lesions from bone scans from a previous assessment
  • Serum testosterone concentration less or equals 50 ng/dL
  • World Health Organization (WHO) performance status 0 to 1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.
  • Sexually active males should be willing to use condoms
  • For inclusion in the AZD3514 administered in combination with abiraterone acetate cohort(s), patients must:
  • Have received prior chemotherapy containing or based on docetaxel
  • Not have received prior treatment with abiraterone acetate, MDV3100, TAK700, TOK001 or other similar therapies which target the AR axis or with selective AR down-regulator-like properties
  • For inclusion in the AZD3514 administered in combination with abiraterone acetate in patients who are currently receiving abiraterone acetate cohort(s), patients must:

    1. Have been stable on abiraterone acetate abiraterone acetate for ≥ 4 months (i.e. stable PSA values) and have achieved ≥ 50% reduction in PSA while being treated with abiraterone acetate
    2. Have evidence of biochemical progression (PSA) of the prostate cancer, as defined in inclusion number 5 (except for the withdrawal of abiraterone acetate as an anti-androgen therapy)
  • For inclusion in the paired (same lesion) tumour biopsy research, patients must:

    1. Provide informed consent for paired tumour biopsy sampling
    2. Have bone or soft tissue lesions that are suitable for paired biopsy sampling

Exclusion Criteria:

  • Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAEv4) grade 1 except for alopecia or toxicities related to the use of gonadotropin-releasing hormone agonists
  • Medically important spinal cord compression or brain metastases
  • Medically important evidence of severe or uncontrolled systemic disease
  • History of hypersensitivity to active or inactive excipients of AZD3514 or drugs with a similar chemical structure or class to AZD3514
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD3514
  • Inadequate bone marrow reserve or organ function
  • Any medically important factors identified from electrocardiogram (ECG) measurements
  • Concurrent or recent treatment with certain medications or medical procedures

The following criteria exclude patients from entering the AZD3514 administered in combination with abiraterone acetate cohort(s):

  • As judged by the investigator, any evidence of severe or uncontrolled systemic diseases or conditions, including adrenocortical insufficiency or a history of cardiovascular disease including heart failure (currently there are no randomized data for the use of abiraterone acetate in patients with LVEF < 50% or NYHA Class III or IV heart failure), which would make it undesirable for the patient to participate in the trial. See the full local prescribing information for abiraterone acetate for more detail
  • Child-Pugh class B and C hepatic impairment
  • If unable to fast for ≥ 2 hours prior to taking a dose to ≥ 1 hour post dose
  • Received abiraterone acetate treatment previously
  • Known hypersensitivity to components of prednisone or prednisolone
  • Any systemic fungal infections
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 20 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01162395
Other Study ID Numbers  ICMJE D3760C00001
2010-020232-19 ( EudraCT Number )
IND 111707
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tony Elliott, MD The Christie Hospital
Study Director: Glen Clack, MD AstraZeneca
PRS Account AstraZeneca
Verification Date January 2016

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