A trial of the combination treatment enzalutamide and AZD5363 for patients with advanced prostate cancer.

• Conditions: Metastatic Castration- Resistant Prostate Cancer; MedDRA version: 16.1Level: PTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-004091-34-GB
• Lead Sponsor: The Royal Marsden NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-27
• Last Update Posted: 7 April 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 136

Inclusion Criteria

1)Written informed consent.
2)Histological diagnosis of adenocarcinoma of the prostate and with archival tumour tissue
3)Metastatic Castration-Resistant Prostate Cancer (mCRPC).
4)Progressed after 1 or 2 lines of taxane based chemotherapy.
5)Progressed after at least 12 weeks of abiraterone
6)Age 18 years or above.
7)Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
8)PSA greater than or equal to 10ng/ml.
9)Documented willingness to use an effective means of contraception while participating in the study and for 12 months post last dose of treatment
10)Documented ongoing castrate serum testosterone <50 ng/dL (<2.0 nM).
11)Received prior castration by orchiectomy and/or ongoing Luteinizing Hormone-Releasing Hormone (LH-RH) agonist treatment.
12)Progression of disease by PSA utilizing PCWG2 criteria and at least another of the following criteria;
a.disease progression as defined by at least 2 new lesions on bone scan.
b.Soft tissue disease progression defined by modified RECIST 1.1.
c.Clinical progression (worsening pain & the need for palliative radiotherapy).

PHASE I SAFETY RUN IN and EXPANSION COHORT - inclusion criteria:
13)Willing to have a biopsy to obtain tumour tissue for biomarker analyses prior to and after treatment.

SINGLE STAGE PHASE II EXPANSION COHORT ONLY - inclusion criteria:
14)Prior exposure to enzalutamide of at least 12 weeks is required with documented disease progression
15)Archival tumour tissue available for the analysis of PTEN loss by the central laboratory

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

1)Prior treatment with enzalutamide (not applicable for the phase I safety run in or for the single stage phase II expansion cohort).
2)Prior treatment with PI3K, AKT, TOR kinase or mTOR inhibitors
3)Surgery, chemotherapy, or other anti-cancer therapy within 4 weeks prior to trial entry / randomisation into the study (6 weeks for bicalutamide). Any other therapies for prostate cancer, other than GnRH analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol), or 5-alpha reductase inhibitors (e.g., finasteride or dutasteride), must be discontinued at least 2 weeks before the first dose of study drug.
4)Participation in another clinical trial and any concurrent treatment with any investigational drug within 4 weeks prior to trial entry / randomisation.
5)Prior limited field radiotherapy within 2 weeks or wide field radiotherapy within 4 weeks of trial entry / randomisation.
6)History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumours, brain metastases, or alcoholism.
7)History of loss of consciousness or transient ischemic attack within the previous 12 months of trial entry / randomisation.
8)Known brain or leptomeningeal involvement.
9)Use of potent inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 2 weeks before trial entry / randomisation (3 weeks for St John¡¯s Wort) must be avoided.
10)Clinically significant abnormalities of glucose metabolism as defined by any of the following:
a.Diagnosis of diabetes mellitus type I or II
b.Glycosylated haemoglobin (HbA1C) =8.0% at screening
c.Fasting Plasma Glucose =8.9mmol/L at screening.
11)Inadequate organ and bone marrow function as evidenced by:
a.Haemoglobin <8.5 g/dL
b.Absolute neutrophil count <1.0 x 109/L
c.Platelet count < 75 x 109/L
d.Albumin =25 g/dL.
e.AST / SGOT and/or ALT / SGPT = 2.5 x ULN (=5 x ULN if liver metastases)
f.Total bilirubin = 1.5 x ULN (except for patient with Gilbert's disease)
g.Serum Creatinine > 1.5 x ULN
12)Inability or unwillingness to swallow oral medication.
13)Malabsorption syndrome or other condition that would interfere with enteral absorption.
14)Any of the following cardiac criteria;
a.Mean resting corrected QT interval (QTcF) >470msec obtained triplicate ECGs
b.Clinically important abnormalities(rhythm/conduction/morphology)resting ECG
c.Factors that increase risk of QTc prolongation or risk of arrhythmic events
d.Experience of any of the following in the preceding six months:
- coronary artery bypass graft
- angioplasty
- vascular stent
- myocardial infarction
- angina pectoris
- congestive heart failure NYHA = Grade2
e.Uncontrolled hypotension
15)Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
16)Any other finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patients at high risk from treatment complications.
17)Need for chronic corticosteroid therapy of >10 mg of prednisolone or >0.5mg of dexamethasone per day or an equivalent dose of other anti inflammatory corticosteroid.
18)Malignancies other than prostate cancer within 5 years prior to trial ent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified