Open Label Prostate Cancer Study

January 11, 2016 updated by: AstraZeneca

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.

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

64

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Research Site
  • United Kingdom
      • Glasgow, United Kingdom
        • Research Site
      • Manchester, United Kingdom
        • Research Site
      • Surrey, United Kingdom
        • Research Site
  • United States
    • Oregon
      • Portland, Oregon, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Ascending doses of AZD3514 administered orally to patients to define the maximum tolerated dose (MTD)
Drug: AZD3514
Patients will be given AZD3514 orally as a single dose, and then multiple once daily dosing following a 5-9 day washout.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To investigate the safety and tolerability of AZD3514 when given orally to patients with CRPC.
Time Frame: At every visit.
At every visit.

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
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.
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
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
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
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
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
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
July 2012 - Feb 2013

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Study Director: Glen Clack, MD, AstraZeneca
  • Principal Investigator: Tony Elliott, MD, The Christie Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

July 13, 2010

First Submitted That Met QC Criteria

July 13, 2010

First Posted (Estimate)

July 14, 2010

Study Record Updates

Last Update Posted (Estimate)

January 12, 2016

Last Update Submitted That Met QC Criteria

January 11, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D3760C00001
  • 2010-020232-19 (EudraCT Number)
  • IND 111707

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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