S1216:A Phase III Randomized Trial Comparing Androgen Deprivation Therapy + TAK-700 with Androgen Deprivation Therapy + Bicalutamide in Patients with Newly Diagnosed Metastatic Hormone Sensitive Prostate Cancer

Summary

The purpose of this study is to find out what effects (good and/or bad) there are to adding
the new investigational drug TaK-700 (also called orteronel) to standard hormone therapy
which is used to treat prostate cancer as compared to the standard of hormone therapy
alone. The combination of TaK-700 and standard hormone therapy is considered
experimental.

The subject will be [Quote]randomized[Quote] into one of the study groups described below.

Subjects in Group 1 (often called [Quote]arm 1[Quote]) will receive standard hormone therapy plus
TaK-700. Leuprolide acetate (Lupron) or goserelin acetate (Zoladex) will be given as a shot in
the muscle once every 3 months. The subject will take TaK-700 as a tablet twice every day.

if the subject has not received hormone therapy before and have pain from the cancer, the subject will
take TaK-700 for seven days before receiving leuprolide acetate (Lupron) or goserelin acetate
(Zoladex). if you have no pain, you may start TaK-700 on the same day as leuprolide acetate
(Lupron) or goserelin acetate (Zoladex).

Subjects in Group 2 (often called [Quote]arm 2[Quote]) will receive standard treatment with hormone
therapies. Leuprolide acetate (Lupron) or goserelin acetate (Zoladex) will be given as a shot in
the muscle once every 3 months. You will take bicalutamide (Casodex) as a tablet
once every day. This is standard hormone therapy will be giveneven if the subjects
were not in this research study. if the subject has received hormone therapy before and have
pain from the cancer, the subject will take bicalutamide (Casodex) for seven days before receiving
leuprolide acetate (Lupron) or goserelin acetate (Zoladex). if the subject has no pain, the subject may start
bicalutamide (Casodex) on the same day as leuprolide acetate (Lupron) or goserelin acetate
(Zoladex).

Participant Eligibility

There are two patient populations eligible for the study: those who have not started any therapy
with LHRH agonist or antagonist (or orchiectomy) (Early Induction Group) and those who have already started therapy with LHRH agonist or antagonist (or orchiectomy) within the 30 days prior to registration (Late Induction Group). Subjects must be registered within 30 days of first injection of the LHRH agonist or antagonist (or orchiectomy).

Disease Related Criteria:
- All patients must have a histologically or cytologically proven diagnosis of
adenocarcinoma of the prostate. All patients must have distant metastatic
disease as evidenced by soft tissue and/or bony metastases prior to initiation of
androgen deprivation therapy.
-
* Patients who will not have an LHRH injection until after randomization
(early induction group) must have radiographic assessments of all disease
including bone scan (or PET scan) within 42 days prior to registration. Patients
who have started androgen deprivation therapy (LHRH agonist/antagonist or
orchiectomy) prior to registration (late induction group) must have radiographic
assessments including bone scan (or PET scan) within 42 days prior to first
LHRH injection. (If scans have not been obtained prior to LHRH
agonist/antagonist or orchiectomy they must be done within 42 days prior to
registration). All disease must be assessed and documented on the Baseline
Tumor Assessment Form.
*

Prior Therapy Criteria:
- Patients may have received prior androgen deprivation therapy (ADT)
- neoadjuvant and/or adjuvant hormonal therapy setting only, but it must not
have lasted for more than 36 months. Single or combination therapy allowed.
At least 6 months must have elapsed since completion of androgen
deprivation therapy in the neoadjuvant and/or adjuvant setting, and serum
testosterone must be within institutional limits of normal > 50 ng/mL (noncastrate
levels) at the time of registration for early induction patients. Note:
Serum testosterone assessment is required for eligibility for only those with
prior treatment with ADT
- Patients may have received palliative radiotherapy for symptomatic bone or
visceral metastasis and patients must have recovered from all side effects prior to registration. Concomitant radiotherapy will be allowed only for baseline symptoms (e.g. primary prostate related urinary symptoms and bone pain) per investigator[Single Quote]s clinical judgment during the first 4 months
of protocol treatment.
- Patients may have received prior surgery. For all major surgeries, at least 14
days must have elapsed since completion and patient must have recovered from
all major side effects of surgery per investigator[Single Quote]s assessment.
- Patients may have received or plan to receive concurrent bone targeting agents
that do not have an effect on PSA (e.g. denosumab or bisphosphonate).
- Patients with no plans to receive any other experimental therapy while on
the protocol treatment. Previous experimental therapy must have been
completed at least 28 days prior to registration.
- In the late induction group, patients must have had no more than 30 days of prior castration (medical or surgical) for metastatic prostate cancer prior to registration. The start date of medical castration is considered the day the patient first received an injection of a LHRH agonist/antagonist (or orchiectomy), not an oral antiandrogen.
If the method of castration was luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide or goserelin), the patient must be willing to continue the use of LHRH agonist and add bicalutamide or TAK-700 (according to randomization) during protocol treatment.
If the patient was on an antiandrogen (e.g. bicalutamide, flutamide), the patient must be willing to switch over to bicalutamide or TAK-700 (according to randomization). No washout is required.
If the method of castration was LHRH antagonists (i.e. Degarelix), the patient must be willing to switch to an LHRH agonist during protocol treatment.

Clinical/Laboratory Criteria:
- Patients must have a PSA >= 2 ng/mL obtained within 90 days prior registration.
- A DEXA scan must be obtained within 2 years prior to registration.
- Patients must not have any Grade III/IV cardiac disease as defined by the New
York Heart Association Criteria (i.e., patients with cardiac disease resulting in
marked limitation of physical activity or resulting in inability to carry on any
physical activity without discomfort), thromboembolic event, unstable angina
pectoris, myocardial infarction within 6 months, or serious uncontrolled cardiac
arrhythmia. See Appendix 18.4.
- Patients must have a QTc interval < 461 msec on the 12 lead ECG within 42 days
prior to registration.
- Patients must have a left ventricular ejection fraction (LVEF) >50% by echocardiogram or MUGA within 42 days prior to registration.
-Patients must have blood pressure measured within 14 days prior to registration.
Patients must not have uncontrolled hypertension (defined as blood pressure >
160 mmHg systolic and > 90 mmHg diastolic at 2 separate measurements no
more than 60 minutes apart) despite appropriate medical therapy. Note: Patients
may be rescreened after adjustments of antihypertensive medications. See
ACCF/AHA.AMA-PCPI joint statement.
- Patients must have adequate hepatic function as evidenced by bilirubin <= 2 x
institutional upper limit of normal (ULN), SGOT (AST) and SGPT (ALT) <= 3 x
institutional ULN, or <= 5 x institutional ULN if liver metastases are present. These
results must be obtained within 28 days prior to registration.
- Patients must have adequate renal function as evidenced by calculated creatinine
clearance >= 40 mL/min using a serum creatinine obtained within 28 days prior to
registration.
- Patients must have adequate hematologic function as evidenced by leukocytes >=
3,000/mcL, absolute neutrophil count (ANC) >= 1,500/mcL, hemoglobin >= 9 g/dL,
and platelets >= 100,000/mcL. These results must be obtained within 28 days
prior to registration.
- Patients must have a Zubrod performance status of 0 - 2. Zubrod performance status 3 will be allowed if from bone pain only.
- Patients must be >= 18 years of age.
- Men of reproductive potential and those who are surgically sterilized (i.e., postvasectomy)
must agree to practice effective barrier contraception or agree to
abstain from intercourse while receiving treatment on this study and for at least 4
months after protocol treatment ends.

Regulatory Criteria:
- Patients must be offered the opportunity to participate in specimen banking for
future use to include translational medicine studies.
- Patients or their legally authorized representative must be informed of the
investigational nature of this study and must sign and give written informed
consent in accordance with institutional and federal guidelines. Voluntary written informed consent must be obtained before performance of any
study-related procedure not part of normal medical care, with the understanding
that consent may be withdrawn by the patient at any time without prejudice to
future medical care.