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
- Conditions
- castrate-resistant prostate cancerProstate Cancer10038597
- Registration Number
- NL-OMON34099
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 17
- Provision of signed and dated written informed consent
- Males aged 20 years or older
- Histologically or cytologically proven prostate cancer for which no standard therapy is currently considered appropriate
- Documented evidend of metastatic prostate cancer
- Presence of progressive disease as defined as one or more:
* Biochemical progression of the prostate cancer, defined as at least 2 stepwise increases in a series of any 3 PSA values collected while patient is castrate. The 3 PSA values selected do not need to be consecutive, and do not need to include the most recent PSA collected at, or prior to, study enrolment but must meet the following criteria:
i. There must be at least 14 days between each of the 3 PSA values, and each must be collected no more than 1 year before enrolment into the study
ii. The last PSA value in the series of the 3 must be either an increase of > 25% of the first PSA or an absolute increase of >10 ng/mL over the first PSA
iii. The last PSA value in the series of 3 must be > 1.2 ng/mL in patients who have had a radical prostatectomy and > 5 ng/mL in all other patients
iv. Each of the 3 PSA values must be collected whilst the patient is under medical castration or is surgically castrated
v. All PSA increases should be recorded after withdrawal of anti-androgen therapy
vi. All 3 PSA values must have been acquired after commencement of the last line of systemic therapy, including corticosteroids regardless of the therapeutic intent
* Progression as defined by RECIST 1.1
* Two or more new metastatic bone lesions from bone scans from a previous assessment
- Serum testosterone concentration < 50 ng/dL
- WHO performance status 0 to 1
- Patients should use condoms
- Treatment with any of the following:
* Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
* Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment
* Any previous exposure to a selective androgen-receptor down-regulator
* Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of
study treatment
* Any hormonal therapy (e.g. steroids) within 4 weeks of the first dose of study treatment (6 weeks
for anti-androgens). The use of LHRH-analogues is permitted. Concomitant use of steoids e.g. including but not limited to prednisolone, prednisone or dexamethasone is permitted if being administered as a supportive care agent
* Potent inhibitors or inducers of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St John*s Wort)
* AZD3514 in the present study
* Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study
treatment
*Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of
radiation for palliation within 2 weeks of the first dose of study treatment
- With the exception of alopecia or toxicities related to the use of gonadotropin-releasing hormone
agonists, any unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAEv4) grade 1 at the time of starting study treatment
- Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not
requiring steroids for at least 4 weeks prior to start of study treatment
- As judged by the investigator, any evidence of severe or uncontrolled systemic diseases,
including uncontrolled hypertension, active bleeding diatheses, or active infection including
hepatitis B, hepatitis C and HIV.
- Any of the following cardiac criteria (see protocol)
- Inadequate bone marrow reserve or organ function as demonstrated by any of the following
laboratory values:
* Absolute neutrophil count < 1.5 x 109/L
* Platelet count < 100 x 109/L
* Haemoglobin < 90 g/L
* Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no demonstrable liver
metastases or > 5 times ULN in the presence of liver metastases
* Aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5 times
ULN in the presence of liver metastases
* Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of liver
metastases
* Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min (measured or
calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required
when creatinine is > 1.5 times ULN
- 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
- History of hypersensitivity to active or inactive excipients of AZD3514 or drugs with a similar
chemical structure or class to AZD3514
- Judgment by the investigator that the patient should not participate in the study if the patient is
unlikely to comply with study procedures, restrictions and requirements
- Involvement in the planning and conduct of the s
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To investigate the safety and tolerability of AZD3514 </p><br>
- Secondary Outcome Measures
Name Time Method <p>To characterise the pharmacokinetics of AZD3514<br /><br>To obtain a preliminary assessment of the anti-tumour activity by evaluation of<br /><br>the tumour response using RECIST 1.1<br /><br>To obtain an assessment of the activity of AZD3514 on the circulating levels of<br /><br>PSA<br /><br>To obtain a preliminary assessment of the anti-tumour activity of AZD3514 by<br /><br>evaluation of counts of circulating tumour cells</p><br>