Open Label Prostate Cancer Study

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01162395
First received: July 13, 2010
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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)


Condition Intervention Phase
Prostate Cancer
Drug: AZD3514
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • To investigate the safety and tolerability of AZD3514 when given orally to patients with CRPC. [ Time Frame: At every visit. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
  • To characterise the PK of AZD3514 after a single oral dose and at steady state after multiple oral doses. [ Time Frame: After each Cohort. ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 64
Study Start Date: August 2010
Estimated Study Completion Date: July 2014
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01162395

Locations
United States, Oregon
Research Site
Portland, Oregon, United States
Netherlands
Research Site
Amsterdam, Netherlands
United Kingdom
Research Site
Glasgow, United Kingdom
Research Site
Manchester, United Kingdom
Research Site
Surrey, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Tony Elliott, MD The Christie Hospital
Study Director: Glen Clack, MD AstraZeneca
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01162395     History of Changes
Other Study ID Numbers: D3760C00001, 2010-020232-19, IND 111707
Study First Received: July 13, 2010
Last Updated: March 27, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Prostate Cancer
Tumour
Castration Resistant
Prostate Androgen Receptor Down Regulator
Metastatic

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on April 15, 2014