Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.
Anahtar kelimeler
Öz
Açıklama
A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity, Safety, Tolerability, and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) (PYRUS)
Tarih
| Son Doğrulandı: | 05/31/2014 |
| İlk Gönderilen: | 09/18/2012 |
| Tahmini Kayıt Gönderildi: | 09/20/2012 |
| İlk Gönderilen: | 09/24/2012 |
| Son Güncelleme Gönderildi: | 06/17/2014 |
| Son Güncelleme Gönderildi: | 06/18/2014 |
| Fiili Çalışma Başlangıç Tarihi: | 10/31/2012 |
| Tahmini Birincil Tamamlanma Tarihi: | 05/31/2014 |
| Tahmini Çalışma Tamamlanma Tarihi: | 05/31/2014 |
Durum veya hastalık
Müdahale / tedavi
Drug: Part A Group 1 Intermittent
Drug: Part A Group 2 Intermittent
Drug: Part B
Evre
Kol Grupları
| Kol | Müdahale / tedavi |
|---|---|
| Experimental: Part A Group 1 Intermittent Recruitment suspended and will not be re-opened. See intervention description below. | Drug: Part A Group 1 Intermittent 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. |
| Experimental: Part A Group 2 Intermittent Recruitment complete. See intervention description below. | Drug: Part A Group 2 Intermittent Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue to study withdrawal. Recruitment complete. |
| Experimental: Part B This part of the study will not be conducted following a review of data from Part A. See intervention description below. | Drug: Part B Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue until study drug withdrawal. This part of the study will not be conducted. |
Uygunluk kriterleri
| Çalışmaya Uygun Yaşlar | 18 Years İçin 18 Years |
| Çalışmaya Uygun Cinsiyetler | Male |
| Sağlıklı Gönüllüleri Kabul Ediyor | Evet |
| Kriterler | Inclusion Criteria: - 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; Exclusion Criteria: - 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 |
Sonuç
Birincil Sonuç Ölçütleri
1. 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]
2. 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]
3. 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]
4. 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.]
İkincil Sonuç Ölçütleri
1. 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.]
2. 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]
3. 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]
4. 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.]
5. Parts A and B: Quality of life (QoL) [QOL will be documented from date of randomization and for 12 weeks.]
