A Phase 1/2, Open-Label Study in Men with Prostate Cancer to Assess the Safety, Pharmacokinetics, and Testosterone-Lowering Efficacy of TAK-448, Administered as a 1 Month Depot, Including a Randomized Portion With a Group Administered Leuproreli
- Conditions
- Prostate cancerMedDRA version: 12.1Level: LLTClassification code 10007113Term: Cancer of prostate
- Registration Number
- EUCTR2009-017668-18-FR
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 0
The following criteria must be met by each patient to be eligible for the phase 1 or phase 2 portion of the study, unless otherwise specified:
1. Male 40 to 72 years of age, inclusive.
2. Histologically-confirmed adenocarcinoma of the prostate, having completed primary local treatment at least 6 months prior to screening.
3. Screening serum PSA concentration > 2 ng/mL.
4. For the phase 1 portion of the study only: Either
a) Concurrent GnRH therapy with generally indolent or stable disease with PSA DT >6 months and absolute PSA <30 ng/mL and if metastatic disease, asymptomatic with only bone scan positive evidence of metastases. Patients with recurrent local disease will be 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, i.e. in a period of ‘watchful waiting’ with generally indolent or stable disease with PSA DT >6 months and absolute PSA <30 ng/mL, and if metastatic disease, asymptomatic with only bone scan positive evidence of metastases. Patients with
recurrent local disease will be asymptomatic without bladder, bowel, or obstructive symptoms.
5. 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 for adjuvant/neoadjuvant therapy as part of local treatment of disease (surgery or radiation) or for primary local tumor control.
6. 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.
7. Generally fit medical condition, with no acute or chronic medical conditions, other than prostate cancer, affecting 2 year life expectancy.
a) ECOG performance status 0 or 1
b) New York Heart Association classification 0 to II
c) Serum creatinine < 1.5 ULN
d) If hypertensive, 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 must be <1.5 x ULN
g) Generally normal laboratory evaluation, liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT]) within 2 times the ULN as reported by the central reference laboratory.
8. Ability to understand and comply with protocol requirements.
9. Agreement to, even if surgically sterilized but not surgically castrated (i.e. status postvasectomy):
- Practice effective barrier contraception:
Phase 1 portion of the study: during the entire study treatment period and through 3 months after the dose of study drug
Phase 2 portion of the study: during the entire study treatment period through 2 months after the last dose of study drug
OR
- Abstain from heterosexual intercourse
10. Suitable venous access for the study-required blood sampling, i.e. including PK and pharmacodynamic sampling.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Nu
1. Advanced or symptomatic metastatic prostate cancer requiring immediate GnRH or
additional hormone (CAB) therapy or requiring chemotherapy
2. History of surgical castration
3. Any history of nonskin cancer, other than prostate cancer, requiring active treatment within the 2 years prior to screening
4. Any history of cardiac surgery, within the previous 6 months or any planned elective surgeries, other than skin surgery, during the ensuing 6 months
5. Any compromise of bone marrow function that would reduce tolerance to repeated
blood draws
6. Any history of osteoporosis, unless actively controlled with treatment, or history of
vertebral or femoral fracture within the past year
7. Any history of seizures or currently on anticonvulsant medications
8. Any history of major psychiatric illness, eg, diagnosed psychosis or psychiatric
illness requiring hospitalization within the previous year
9. Any history of drug or significant alcohol abuse
10. Any participation in clinical trials or receipt of any experimental therapy within
2 months of screening
11. Serious infection within 14 days before the first dose of study drug
12. Known human immunodeficiency virus positive
13. Known hepatitis B surface antigen-positive (HBsAg), or known or suspected active hepatitis C infection
14. Any of the following cardiovascular conditions or values at the time of screening
unless otherwise specified:
• History of myocardial infarction, unstable symptomatic ischemic heart
disease, ongoing arrhythmias of grade > 2 ( CTCAE version 4.02(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.
• QTc > 500 milliseconds.
• 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.
In addition, for the phase 2 portion of the study, patients must not have any of the
following exclusion criteria:
15. Participation in the phase 1 portion of the study
16. Prior or current use of a GnRH analog or androgen receptor antagonist as first-line hormone therapy (ie, other than as neoadjuvant/adjuvant use)
17. History of use of GnRH analog or antagonist (as adjuvant or neoadjuvant therapy) within the 6 months prior to screening
18. History of known or documented primary failure of GnRH analog therapy
19. History of rising PSA or disease progression while on a GnRH analog or CAB
therapy (ie, rising PSA while on neoadjuvant/adjuvant therapy)
20. Screening serum testosterone concentration < 150 ng/dL (5.25 nmol/L)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method