Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.

NCT01692262 | Completed Phase 1

• 2 other identifiers: D3610C00003GU86
• Study Type: interventional
• Target: 59
• Locations: 2 countries
• Sites: 8

Brief Summary

To investigate the safety, tolerability and anti-tumour activity of AZD5363, as monotherapy, in patients with metastatic Castrate-Resistant Prostate Cancer. AZD5363 will be investigated in patients who have progressed after chemotherapy (Part A) and in patients who have progressed before receiving chemotherapy (Part B). Recruitment into Part A, Group 1 has been suspended. A new design for this group is currently being evaluated. Part A, group 2 patients (progressed after 1 or more 2nd generational anti-hormonal therapies) will receive AZD5363 480mg bid intermittently (4 days on/3days off). Part B will only start if there is evidence of anti-tumour activity along with AZD5363 having an acceptable safety profile in Part A. Part B will be conducted in pre-chemotherapy patients on a dose and schedule selected from Part A.

Conditions

Metastatic Castrate-Resistant Prostate Cancer (mCRPC),; Efficacy,; Safety and Tolerability,; Pharmacokinetics,; Pharmacodynamics,; Tumour Response.

Keywords

Metastatic Castrate-Resistant Prostate Cancer (mCRPC),; adenocarcinoma of the prostate,; prostate cancer,; progressive disease,; advanced disease.

Outcome Measures

Primary Outcomes (4)

• Parts A and B: Anti-tumour activity by measurement of changes in circulating prostate-specific antigen (PSA)

  PSA measured from baseline for every 4 weeks. Primary assessment is at 12 weeks

• Parts A and B: Anti-tumour activity by measurement of changes in circulating tumour cells (CTC)

  CTC measured from baseline for every 4 weeks to week 12 (primary assessment) then measured every 12 weeks

• Parts A and B: Anti-tumour activity by measurement of malignant soft tissue response rate

  Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent

• Parts A and B: Anti-tumour activity by measurement of metastatic bone disease status

  Bone lesion assessments by bone scan (PCWG2) criteria every 12 weeks from baseline up to disease progression or withdrawal of consent.

Secondary Outcomes (5)

• Parts A and B: Safety and tolerability of AZD5363 in terms of adverse events, serious adverse events (including death) and safety measures: ECG, ECHO/MUGA, physical examination, pulse, blood pressure, weight and laboratory variables

  Routine safety assessments, throughout the period that patients receive AZD5363 up to 28 days following discontinuation of study treatment.

• Parts A and B: AZD5363 PK: time to maximum plasma concentration, terminal rate constant,terminal half life, area under plasma concentration time curve, plasma clearance & volume of distribution

  Multiple AZD5363 PK blood sample assessments.AZD5363 plasma concentration blood samples will be taken on Day 1(pre-dose,2,4,8 hours post-dose);D2(pre-dose);D8(continous) or D11(intermittent) (pre-dose and at 2,4,and 8 hours post-dose);D15,Cyc

• Parts A and B: Plasma concentrations of pharmacodynamic (PD) biomarker

  Multiple PD blood sample assessments.PD blood samples will be taken on the same schedule as PK sample and then Day 1 of every 12 weeks thereafter, and at the discontinuation visit

• Parts A and B: Progression-free survival (PFS)

  Tumour assessments by RECIST v1.1 every 12 weeks from baseline up to disease progression or withdrawal of consent.

• Parts A and B: Quality of life (QoL)

  QOL will be documented from date of randomization and for 12 weeks.

Study Arms (3)

Part A Group 1 Intermittent

EXPERIMENTAL

Recruitment suspended and will not be re-opened. See intervention description below.

Drug: Intermittent dosing of AZD5363

Part A Group 2 Intermittent

EXPERIMENTAL

Recruitment complete. See intervention description below.

Drug: Intermittent dosing of AZD5363

Part B

EXPERIMENTAL

This part of the study will not be conducted following a review of data from Part A. See intervention description below.

Drug: Intermittent dosing of AZD5363

Interventions

Intermittent dosing of AZD5363 DRUG

Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Recruitment suspended and will not be re-opened.

Part A Group 1 Intermittent

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent
• Males aged 18 years and older
• Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features for which no standard therapy is currently considered appropriate
• Documented evidence of Metastatic Castrate-Resistant Prostate Cancer (mCRPC)
• Part A: Patients must have received prior docetaxel-based chemotherapy for mCRPC and have a Circulating Tumour Cell score of 5;
• Part B: Patients must have progressed before receiving any chemotherapy for mCRPC;

You may not qualify if:

• Any prior exposure to agents which inhibit AKT as the primary pharmacological activity
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus
• Spinal cord compression or brain metastases unless asymptomatic, treated, and stable and not requiring steroids
• Clinically significant abnormalities of glucose metabolism
• Major surgery within the previous 4 weeks

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (8)

Research Site

Sarasota, Florida, United States

Location

Research Site

Boston, Massachusetts, United States

Location

Research Site

Ann Arbor, Michigan, United States

Location

Research Site

Hackensack, New Jersey, United States

Location

Research Site

Nashville, Tennessee, United States

Location

Research Site

Cardiff, Wales, United Kingdom

Location

Research Site

London, United Kingdom

Location

Research Site

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Disease Progression

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Paul Stockman, MBCHB, PHD

  AstraZeneca

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2012
• First Posted: September 25, 2012
• Study Start: November 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: June 19, 2014

Record last verified: 2014-06

Locations

GB (3); US (5)