Summary

for males ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Mack Roach

Description

Summary

RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as steroid 17alpha-monooxygenase TAK-700, when used with other hormone therapy, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x rays to kill tumor cells. This may be an effective treatment for prostate cancer when combined with hormone therapy. Studying quality-of-life in patients having cancer treatment may help identify the intermediate- and long-term effects of treatment on patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying the use of hormone therapy, including TAK-700, together with radiation therapy in treating patients with prostate cancer.

Official Title

Phase III Trial of Dose Escalated Radiation Therapy and Standard Androgen Deprivation Therapy (ADT) With a GNRH Agonist vs. Dose Escalated Radiation Therapy and Enhanced ADT With a GNRH Agonist and TAK-700 For Men With High Risk Prostate Cancer

Details

OBJECTIVES:

Primary

  • To evaluate the difference in overall survival of patients with clinically localized prostate cancer with unfavorable prognostic features between a) standard treatment (androgen-deprivation therapy [ADT] + radiotherapy) and b) standard treatment with the addition of 24 months of steroid 17alpha-monooxygenase TAK-700 (TAK-700).

Secondary

  • To characterize differences between the treatment groups with respect to incidence of unexpected grade ≥ 3 adverse events and/or clinically significant decrement in patient-reported quality of life (QOL) among subjects treated with TAK-700.
  • To compare rates and cumulative incidence of biochemical control (freedom from PSA failure), local/regional progression, and distant metastases.
  • To compare rate and cumulative incidence of clinical failure, defined as prostate-specific antigen (PSA) > 25 ng/mL, documented local disease progression, regional or distant metastasis, or initiation of ADT.
  • To compare prostate cancer-specific survival and other-cause mortality.
  • To compare the change in severity of fatigue as measured by the Patient-Reported Outcome Measurement Information System (PROMIS) fatigue short form.
  • To compare changes in patient-reported QOL as measured by Expanded Prostate Cancer Index Composite (EPIC).
  • To assess quality-adjusted survival using the EQ-5D.
  • To compare nadir and average serum testosterone at 12 and 24 months during treatment.
  • To compare changes in hemoglobin A1C, fasting glucose, and fasting insulin during 24 months of systemic treatment and during the first three years of follow-up.
  • To compare changes in fasting lipid levels during 24 months of treatment and during the first three years of follow-up.
  • To compare changes in body mass index (BMI) during 24 months of treatment and during the first three years of follow-up.
  • To compare the incidence of adverse events ascertained via CTCAE version 4.
  • To compare the rate of recovery of testosterone to > 230 ng/dL (accepted threshold for supplementation) after 12 and 24 months of follow-up.
  • To compare the median time to recovery of testosterone to > 230 ng/dL during the first five years of follow-up.
  • To assess cumulative incidence of relevant clinical survivorship endpoints including new diagnosis of type 2 diabetes, coronary artery disease, myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, or osteoporotic fracture.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to risk group (see Disease Characteristics) and type of radiation therapy (RT) boost (intensity-modulated RT (IMRT) vs brachytherapy). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive standard androgen suppression (AS) with a luteinizing hormone-releasing hormone (LHRH) agonist (such as leuprolide, goserelin, buserelin, or triptorelin) for 24 months from initiation and oral (PO) antiandrogen (such as flutamide or bicalutamide) beginning 2 months prior and for the duration of radiation therapy (RT).
  • Arm II: Patients receive the same standard AS with LHRH agonist and oral antiandrogen as in arm 1. Patients also receive steroid 17alpha-monooxygenase TAK-700 (TAK-700) PO twice daily (BID) for 2 years.

In both arms, patients undergo IMRT or 3D-conformal RT to the whole pelvis once daily, 5 days a week, for 6-8 weeks. Some patients also receive brachytherapy.

Quality of life is assessed via the Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale, the Expanded Prostate Cancer Index Composite (EPIC-26), and the EuroQol (EQ-5D) assessments at baseline and periodically during the study.

Serum may be collected from some patients for correlative studies.

After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.

Keywords

Prostate Canceradenocarcinoma of the prostatestage I prostate cancerstage IIA prostate cancerstage IIB prostate cancerstage III prostate cancerstage IV prostate cancerProstatic NeoplasmsLeuprolideBuserelinGoserelinTriptorelin PamoateFlutamideBicalutamideDeslorelingoserelin acetateleuprolide acetateorteroneltriptorelinADT + GnRH agonist + dose escalated radiationADT + GnRH agonist + dose escalated radiation + TAK-700

Eligibility

For males ages 18 years and up

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days prior to registration at high risk for recurrence as determined by one of the following combinations (risk group):
  • Gleason Score (GS) ≥ 9, PSA ≤ 150 ng/mL, any T stage
  • GS ≥ 8, PSA < 20 ng/mL, T stage ≥ T2
  • GS ≥ 8, PSA ≥ 20-150 ng/mL, any T stage
  • GS ≥ 7, PSA ≥ 20-150 ng/mL, any T stage
  • Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott, Hybritech), obtained prior to any luteinizing hormone-releasing hormone (LHRH) agonist or antiandrogen therapy, within 180 days of randomization
  • Androgen deprivation therapy (ADT), such as LHRH agonists (e.g., goserelin, leuprolide), anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., diethyl-stilbestrol [DES]), or surgical castration (orchiectomy), may have been started prior to registration, provided that registration is within 50 days of beginning ADT; please note: if the patient has started ADT he will not be eligible to participate in the quality of life component of this study
  • Clinically negative lymph nodes as established by imaging (abdominal and/or pelvic CT or abdominal and/or pelvic MRI), nodal sampling, or dissection within 90 days prior to registration
  • Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are < 2.0 cm
  • No distant metastases (M0) on bone scan within 90 days prior to registration
  • Equivocal bone scan findings are allowed if plain films are negative for metastasis
  • No definite evidence of metastatic disease
  • Any patient undergoing brachytherapy must have transrectal ultrasound confirmation of prostate volume < 60 cc, American Urological Association (AUA) score ≤ 15 within 60 days of registration, and no history of prior transurethral resection of the prostate (TURP)
  • Prior TURP is permitted for patients who receive external-beam radiotherapy (EBRT) only

PATIENT CHARACTERISTICS:

  • Height, weight, Zubrod performance status 0-1
  • Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3

  • Platelets ≥ 100,000 cells/mm3

  • Hemoglobin ≥ 8.0 g/dL (The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
  • Serum creatinine < 2.0 mg/dL
  • Creatinine clearance > 40 mL/minute
  • Bilirubin < 1.5 x upper limit of normal (ULN)
  • Alanine aminotranserase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN
  • No PSA > 150 ng/mL
  • Screening calculated ejection fraction ≥ ULN by multiple-gated acquisition (MUGA) scan or by echocardiogram
  • Androgen deprivation therapy (ADT), such as LHRH agonists (e.g., goserelin, leuprolide), anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or surgical castration (orchiectomy) may have been started prior to registration, provided that registration is within 50 days of beginning ADT.
  • Patients, even if surgically sterilized (i.e., status post vasectomy), must agree to practice effective barrier contraception during the entire study treatment period and for 4 months (120 days) after the last dose of study drug
  • No prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not requiring systemic therapy for a minimum of 3 years
  • No known hypersensitivity to TAK-700 or related compounds
  • No history of adrenal insufficiency
  • No history of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of grade > 2 (NCI CTCAE, version 4.02) thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (e.g., pericardial effusion restrictive cardiomyopathy) within 6 months prior to registration
  • Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed
  • No New York Heart Association Class III or IV heart failure
  • No ECG abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening, or corrected QT (QTc) interval > 460 msec
  • No prior allergic reaction to the drugs involved in this protocol
  • No Cushing syndrome
  • No severe chronic renal disease or chronic liver disease
  • No uncontrolled hypertension despite appropriate medical therapy within 21 days prior to registration (blood pressure of greater than 150 mm Hg systolic and 90 mm Hg diastolic at 2 separate measurements no more than 60 minutes apart during screening visit)
  • No serious infection within 14 days prior to registration
  • No uncontrolled nausea, vomiting, or diarrhea (CTCAE grade ≥ 3) despite appropriate medical therapy at the time of registration
  • No known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-700, including difficulty swallowing tablets

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior testosterone administration is allowed if last administered at least 90 days prior to registration
  • No prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason
  • No prior systemic chemotherapy for prostate cancer
  • Prior chemotherapy for a different cancer is allowed
  • No prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields
  • No previous hormonal therapy for > 50 days
  • No chronic treatment with glucocorticoids within one year
  • No major surgery within 14 days prior to registration
  • No other investigational agent
  • No other anticancer therapy
  • No concurrent hormonal therapies including estrogens or herbal products
  • No concurrent ketoconazole or aminoglutethimide
  • No chronic use of systemic corticosteroids, such as oral prednisone

Locations

  • UCSF-Mount Zion
    San FranciscoCalifornia94115United States
  • Kaiser Permanente Cancer Treatment Center
    South San FranciscoCalifornia94080United States

Lead Scientist

  • Mack Roach
    of randomized controlled treatment trials for clinically localized prostate cancer: implications for active surveillance and the United States preventative task force report on screening? J Natl Cancer Inst Monogr. 2012 Dec; 2012(45):221-9. PMID: 23271777; PMCID: PMC3540886.

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Radiation Therapy Oncology Group
ID
NCT01546987
Phase
Phase 3
Study Type
Interventional
Last Updated