Testing of a new drug in men with prostate cancer that may help lower testosterone levels.

• Conditions: Prostate cancer; MedDRA version: 14.0Level: LLTClassification code 10007113Term: Cancer of prostateSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2009-017668-18-BE
• Lead Sponsor: Millennium Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-09-07
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 123

Inclusion Criteria

-Male 40 to 78 years of age, inclusive, in phase 1; no upper age limit for phase 2, if medical entry criteria are otherwise met.
-Histologically confirmed adenocarcinoma of the prostate, having completed primary local treatment at least 6 months prior to screening.
-Screening serum PSA concentration > 2 ng/mL, unless the patient is on concurrent (or intermittent) GnRH analog therapy, in which case no lower limit is applicable (phase 1).

-For single-dose portion only: Either
a.Concurrent GnRH therapy (which may include patients on intermittent GnRH therapy or patients who are otherwise between injections of GnRH analog therapy) with generally indolent or stable disease with PSA DT > 4 months and absolute PSA < 200 ng/mL and, if metastatic disease is present, asymptomatic with only bone scan positive and/or lymph node evidence of metastases. Patients with recurrent local disease will be generally asymptomatic, without bladder, bowel, or obstructive symptoms.
OR
b.If not receiving GnRH therapy, a potential candidate for GnRH at some time in the future (ie, in a period of ‘watchful waiting,’ with generally indolent or stable disease and with PSA DT > 3 months and absolute PSA < 200 ng/mL, and, if metastatic disease, asymptomatic, with only bone scan positive and/or lymph node evidence of metastases). Patients with recurrent local disease will be generally asymptomatic, without bladder, bowel, or obstructive symptoms.

-For the multiple-dose portion only: Evidence of progressive prostate cancer, which, in the opinion of the referring physician and/or study investigator, warrants the initiation of GnRH analog therapy. Such patients may have either elevated or rising PSA at least 6 months following primary local therapy(ies) or have evidence of metastatic disease not previously treated with GnRH analog therapy. Patients are not eligible for inclusion if they are to receive first line hormone therapy as adjuvant/neoadjuvant therapy for local treatment of disease (surgery or radiation) or for primary local tumor control.

-For the phase 2 portion of the study only: Evidence of progressive prostate cancer, which, in the opinion of the referring physician and/or study investigator, warrants the initiation of GnRH analog therapy. Such patients may have either elevated or rising PSA at least 6 months following primary local therapy(ies) or have evidence of metastatic disease not previously treated with first line hormone (GnRH analog) therapy. Patients are not eligible for inclusion if they are to receive first line hormone therapy as adjuvant/neoadjuvant therapy for local treatment of disease (surgery or radiation) or for primary local tumor control.

-Provision of informed consent and, for the phase 1 portion of the study only, willing to participate in a phase 1 trial with no expectation of therapeutic benefit.
-Generally fit medical condition, with no acute or chronic medical conditions, other than prostate cancer, affecting 2 year life expectancy.
a.Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
b.New York Heart Association classification 0 to II
c.Serum creatinine < 1.5 ULN
d.If previously diagnosed hypertension, on 2 or fewer agents and with blood pressure adequately or well controlled (systolic < 150 mmHg, diastolic < 95 mmHg)
e.Hemoglobin > 11.0 g/dL
f.Total bilirubin < 1.5 x ULN
g.Generally normal laboratory evaluation, including liver function tests
(alanine aminotransferase [A

Exclusion Criteria

-Advanced or symptomatic metastatic prostate cancer requiring immediate GnRH or additional hormone (CAB) therapy or requiring chemotherapy
-History of surgical castration
-Any history of nonskin cancer, other than prostate cancer, requiring active treatment within the 2 years prior to screening
-Any history of cardiac surgery, within the previous 6 months or any planned elective surgeries, other than skin surgery, during the ensuing 6 months
-Any compromise of bone marrow function that would reduce tolerance to repeated blood draws
-Any history of osteoporosis, unless actively controlled with treatment, or history of vertebral or femoral fracture within the past year
-Any history of seizures or currently on anticonvulsant medications
-Any history of major psychiatric illness (eg, diagnosed psychosis or psychiatric illness requiring hospitalization within the previous year)
-Any history of drug or significant alcohol abuse
-Any participation in clinical trials or receipt of any experimental therapy within 2 months of screening, with the exception of participation in the phase 1 single-dose portion of this study
-Serious infection within 14 days before the first dose of study drug
-Known human immunodeficiency virus (HIV) positive
-Known hepatitis B surface antigen-positive (HBsAg), or known or suspected active hepatitis C infection
-Any of the following cardiovascular conditions or values at the time of screening unless otherwise specified:
o History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (CTCAE version 4.03(13)), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion or restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Atrial fibrillation on anticoagulant therapy is not allowed.
o QTc > 500 milliseconds.
o Abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that, in the opinion of the investigator, are considered to be clinically significant.
-For the phase 1 and phase 2 portions of the study only, continuous use of systemic or inhaled glucocorticoids (steroids) for more than 2 weeks in the 3 months prior to enrollment (use of nasal steroids is allowed)
-For the phase 1, multiple-dose and the phase 2 portions of the study only, newly introduced (within the first 3 months) bisphosphonates, calcitonins, or other anti-osteoporotic medications, except calcium and vitamin D supplements; however, prior stable therapy for bone loss/osteoporosis is allowed

In addition, for the phase 1, multiple-dose portion of the study only, patients must not meet any of the following exclusion criteria:
-Prior or current use of a GnRH analog or androgen receptor antagonist hormone therapy

In addition, for the phase 2 portion of the study only, patients must not meet any of the following exclusion criteria:
-Prior or current use of a GnRH analog or androgen receptor antagonist as first line hormone therapy (ie, other than as neoadjuvant/adjuvant use)
-History of rising PSA or disease progression while on a GnRH analog or CAB therapy (ie, rising PSA while on neoadjuvant/adjuvant therapy)

In addition, for the phase 1, multiple-dose portion of the study and the phase 2 portion of the study, patients must not meet any of the following exclusion criteria:
-History of use of GnRH analog or a

Study & Design

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