Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Immune System Diseases

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Central Nervous System Depressants

Other Dietary Supplements

Androgens

Leuprolide

Bicalutamide

Benzocaine

Androgen Antagonists

Hormones

Hormone Antagonists

Tannic Acid

LHRH agonist - given as approved for androgen deprivation at a dose necessary to maintain castrate levels and equivalent to 22.5 mg of Leuprolide IM every 3 months.

TAK-700, 300 mg, PO, twice daily

LHRH agonist - given as approved for androgen deprivation at a dose necessary to maintain castrate levels and equivalent to 22.5 mg of Leuprolide IM every 3 months.

Bicalutamide, 50 mg, PO, q daily

TAK-700

Neeraj Agarwal, M.D.

The purpose of this study is to compare overall survival in newly diagnosed metastatic prostate cancer patients randomly assigned to androgen deprivation therapy (ADT) + TAK-700 versus ADT + bicalutamide.

S1216, Phase III ADT+TAK-700 vs. ADT+Bicalutamide for Metastatic Prostate Cancer

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

https://swog.org/Visitors/Download/Policies/Policy43.pdf

Overall survival is defined as the time from random assignment to the date of death from any cause

Progression Free Survival (PFS) is defined as the time from random assignment to first documentation of PSA progression, radiologic progression, clinical progression, or death, whichever occurred first.

PSA progression is defined as a ≥25% increase AND and absolute increase of at last 2 ng/mL from the nadir PSA (or from baseline PSA if there was no drop in PSA after starting treatment).

Radiologic progression is defined as two or more new lesions on radionuclide bone scans.

Clinical progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Prostate-specific antigen (PSA) response rates were divided into complete response (CR: PSA \< 0.2 ng/mL), partial response (PR: PSA between 0.2 and 4.0 ng/mL), and no response (NR: PSA \> 4.0 ng/mL) at a 7-month landmark after random assignment.

Only adverse events that are possibly, probably or definitely related to study drug are reported. Adverse events are graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0) where grade refers to the severity of the AE.

Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care.

Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

Long-term survival is defined as the time from random assignment to the date of death from any cause

Millennium Pharmaceuticals, Inc.

National Cancer Institute (NCI)

SWOG Cancer Research Network

1,256 eligible participants who received protocol treatment were evaluable for AEs: 627 on the LHRHa + TAK-700 arm and 629 on the LHRHa + Bicalutamide arm. Adverse Events (AEs) and Serious Adverse Events (SAEs) are reported by CTCAE Version 4.0. All 1,279 participants who started the study, 638 on the LHRHa + TAK-700 arm and 641 on the LHRHa + Bicalutamide arm, were evaluated for All-Cause Mortality.

Experimental: ADT + TAK-700 LHRH agonist - given as approved for androgen deprivation at a dose necessary to maintain castrate levels and equivalent to 22.5 mg of Leuprolide IM every 3 months.

TAK-700, 300 mg, PO, twice daily

LHRHa + TAK-700

Active Comparator: ADT + Bicalutamide LHRH agonist - given as approved for androgen deprivation at a dose necessary to maintain castrate levels and equivalent to 22.5 mg of Leuprolide IM every 3 months.

Bicalutamide, 50 mg, PO, q daily

LHRHa + Bicalutamide

Total

Age, Continuous

Sex: Female, Male

White

Black

Others

Race/Ethnicity, Customized

Missing

Zubrod performance status scores range from 0 to 3, with higher scores reflecting greater disability.

0: Fully active, able to carry on all pre-disease performance without restriction.

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.
2. Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours.
3. Capable of limited self-care, confined to bed or chair more than 50% of waking hours.

Zubrod Performance Status Score

9-10

Gleason scores can range from 2 to 10, but most often range from 6 to 10. A higher Gleason score indicates a more well-differentiated, aggressive tumor.

Gleason Score at Initial Diagnosis

Median PSA Level

Bone Pain

Bone Metastases

Liver Metastases

Other Visceral Metastases

Minimal

Extensive

Disease Severity

Preregistration LHRH Suppression

Bisphosphonate Use at Study Entry

Prior Radical Prostatectomy

Prior Bilateral Orchiectomy

Genitourinary Committee Statistician

Overall Survival

Progression Free Survival

Complete Response

Partial Response

No Response

PSA Response Rates

Abdominal pain

Acute coronary syndrome

Acute kidney injury

Adrenal insufficiency

Adult respiratory distress syndrome

Agitation

Alanine aminotransferase increased

Alkaline phosphatase increased

Allergic reaction

Anaphylaxis

Anemia

Anorexia

Anxiety

Arthralgia

Arthritis

Aspartate aminotransferase increased

Atrial fibrillation

Back pain

Blood bilirubin increased

Bone pain

Cardiac arrest

Cardiac disorders - Other, specify

Cardiac troponin I increased

Chest pain - cardiac

Colitis

Concentration impairment

Confusion

Constipation

Creatinine increased

Death NOS

Dehydration

Depression

Diarrhea

Dizziness

Dysphagia

Dyspnea

Edema limbs

Ejection fraction decreased

Encephalopathy

Erectile dysfunction

Esophagitis

Fall

Fatigue

Fever

Flank pain

Flu like symptoms

GGT increased

Gastric hemorrhage

Gastric ulcer

General disorders and admin site conditions - Other

Generalized muscle weakness

Gynecomastia

Headache

Heart failure

Hematuria

Hepatobiliary disorders - Other, specify

Hip fracture

Hoarseness

Hot flashes

Hyperglycemia

Hyperkalemia

Hypertension

Hypertriglyceridemia

Hyperuricemia

Hypokalemia

Hyponatremia

Hypophosphatemia

Hypotension

Hypoxia

Infections and infestations - Other, specify

Insomnia

Investigations - Other, specify

Joint infection

Laryngeal edema

Left ventricular systolic dysfunction

Leukocytosis

Lipase increased

Lung infection

Lymphocyte count decreased

Mucositis oral

Multi-organ failure

Muscle weakness lower limb

Musculoskeletal and connective tiss disorder - Other

Myalgia

Myocardial infarction

Nausea

Neutrophil count decreased

Obesity

Osteoporosis

Otitis media

Pain

Pancreatitis

Peripheral sensory neuropathy

Platelet count decreased

Pneumonitis

Pruritus

Pulmonary edema

Pulmonary hypertension

Renal calculi

Resp, thoracic and mediastinal disorders - Other

Eligible participants who received at least one dose of protocol treatment

Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Long-term Survival

Overall Study

Spots Global Cancer Trial Database for androgen therapy