Primary:To investigate the safety and tolerability of ascending doses of AZD3514 in patients with metastatic castration resistant prostate cancerSecondary: To assess the pharmacokinetics and preliminary anti-tumour activity of ascending doses of…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate the safety and tolerability of AZD3514
Secondary outcome
To characterise the pharmacokinetics of AZD3514
To obtain a preliminary assessment of the anti-tumour activity by evaluation of
the tumour response using RECIST 1.1
To obtain an assessment of the activity of AZD3514 on the circulating levels of
PSA
To obtain a preliminary assessment of the anti-tumour activity of AZD3514 by
evaluation of counts of circulating tumour cells
Background summary
For many types of cancer there is a need for new agents.
AZD3514 is a new drug that prevents the testosterone alreday present from
acting on prostate tumor cells by accelerating the degradation of some proteins
called Androgen Receptor(AR). AR are located at the surface of the prostate
cancer celles and are critical for testosterone ability to stimulate the growth
of prostate tumours. The development of AZD3514 is therefore predicted as a
therapy for cancers.
AZD3514 has never been given to humans before. The main purpose of this
research is to establish the safety and tolerability of AZD3514 in patients
with metastatic castrate resistant prostate cancer. The obtained information is
important for the further development of the drug and for the treatment of
patients in the future with this drug.
Study objective
Primary:
To investigate the safety and tolerability of ascending doses of AZD3514 in
patients with metastatic castration resistant prostate cancer
Secondary:
To assess the pharmacokinetics and preliminary anti-tumour activity of
ascending doses of AZD3514 in patients with metastatic castration resistant
prostate cancer
Study design
This phase 1 study consists of two parts: dose escalation study and dose
expansion study.
Dose escalation study: a first group of 3-6 patients will start with a single
dose of AZD3514 capsules, followed by a wash out period of 5-9 days. Then
AZD3514 will beadministered once daily for at least 21 days.
When these doses are tolerated well, a next group of 3-6 patients will receive
a higher dose of AZD3514. When this dose is also tolerated well, then the
following group will receive also a higher dose of AZD3514 and so on. In this
way, the maximum tolerated dose will be established.
In the dose expansion study, two cohorts will be expanded to a maximum of 12
evaluable patients per cohort to investigate the safety, tolerability,
pharmacokinetics and preliminary biological activity further. A patient is
evaluable if he/she has taken the once daily dose for 21 days. The patient can
continue with the study as long as the patient receives benefit from the study
medication and there are no medical problems.
Approximately 50 patients will be included into the study. Beside the NKI/AVL
two other site in England will participate. First subject in is planned for 4
August 2010 and Last subject in is planned for 21 September 2010.
Intervention
Day 1: Single dose of AZD3514, followed by a wash out period of 5-9, followed
by a period of at least 21 days of multiple dosing once daily.
Study burden and risks
Patients will have the following assessments during the study: physical
examination, measurement of blood pressure and heart rate, measurement of
length and weight, blood and urine, CT-scan, MRI, bone scan or X-ray and
collection of hair follicles.
Until now AZD3514 has only been administered to animals. The following adverse
events were reported:
- Feeling or being sick (nausea or vomiting), diarrhoea, reduced appetite,
weight loss
- Changes in the organs that make the blood cells that help fight infection,
carry oxygen around the body or help blood to clot
- Kidney abnormalities that may affect how well the kidneys work
- Liver abnormalities, such as changes in blood tests that may indicate how
well the liver is working
- Increases in the level of sugar in the blood
- Prostate gland and seminal vesicle shrinkage
- Lungs - increases in number of cells that usually fight infection
- AZD3514 may stay in the adrenal glands longer than in other organs. No
adrenal gland abnormalities were seen.
Louis Pasteurlaan 5
2719 EE Zoetermeer
NL
Louis Pasteurlaan 5
2719 EE Zoetermeer
NL
Listed location countries
Age
Inclusion criteria
- 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
Exclusion criteria
- 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 study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-020232-19-NL |
| CCMO | NL32630.031.10 |