Hormone Therapy, Radiation Therapy, and Steroid 17alpha-monooxygenase TAK-700 in Treating Patients With High-Risk Prostate Cancer

This study is currently recruiting participants.
Verified April 2014 by Radiation Therapy Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT01546987
First received: March 3, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: bicalutamide
Drug: buserelin
Drug: flutamide
Drug: goserelin acetate
Drug: leuprolide acetate
Drug: orteronel
Drug: triptorelin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: From the date of randomization to the date of death due to any cause. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of unexpected grade ≥ 3 adverse events and/or clinically significant decrement in patient-reported quality of life (PR-QOL) among patients treated with TAK-700 [ Time Frame: From the date of randomization to the date of first documented AE ≥ grade 3 and/or to the date of first clinically significant decrement in patient-reported quality of life (PR-QOL) among patients treated with TAK-700. ] [ Designated as safety issue: Yes ]
  • Rates and cumulative incidence of biochemical control - freedom from PSA failure [ Time Frame: From the date of randomization to the date of first documented biochemical failure by the Phoenix definition (PSA ≥ 2 ng/ml over the nadir PSA) or the initiation of salvage androgen deprivation therapy. ] [ Designated as safety issue: No ]
  • General clinical treatment failure-free interval [ Time Frame: From the date of randomization to the date of first documented general clinical treatment failure defined as: PSA > 25 ng/ml or documented local disease progression or regional or distant metastasis or initiation of androgen deprivation therapy. ] [ Designated as safety issue: No ]
  • Prostate cancer-specific survival and other-cause survival [ Time Frame: From the date of randomization to the date of death due to prostate cancer for prostate cancer-specific survival and to the date of death due to other causes for other-cause survival. ] [ Designated as safety issue: No ]
  • Change in fatigue from baseline to 1 year, as measured by PROMIS [ Time Frame: One year from the date of randomization. ] [ Designated as safety issue: No ]
  • Changes in PR-QOL as measured by EPIC [ Time Frame: From the date of randomization to the week prior to RT start, to the last week of RT and 1 year and 2.5 years after the initiation of therapy. ] [ Designated as safety issue: No ]
  • Assessment of quality-adjusted survival using the EQ-5D [ Time Frame: From the date of randomization to the week prior to RT start, to the last week of RT and 1 year and 2.5 years after the initiation of therapy. ] [ Designated as safety issue: No ]
  • Nadir and average serum testosterone at 12 and 24 months during treatment [ Time Frame: From baseline to 12 months and 24 months of treatment. ] [ Designated as safety issue: No ]
  • Lipid profiles at 12 and 24 months [ Time Frame: From baseline to 12 months and 24 months. ] [ Designated as safety issue: No ]
  • Fasting plasma glucose, fasting plasma insulin, and hemoglobin A1c at 12 and 24 months [ Time Frame: From baseline to 12 months and 24 months. ] [ Designated as safety issue: No ]
  • Changes in body mass index (BMI) during 24 months of treatment and during the first three years of follow-up [ Time Frame: From baseline to 2 years from the start of treatment and after that every year for 3 more years. ] [ Designated as safety issue: No ]
  • Incidence of adverse events ascertained via Common Toxicity Criteria for Adverse Effects (CTCAE) version 4 [ Time Frame: From the start of therapy to 6 months of follow-up. ] [ Designated as safety issue: Yes ]
  • Rate of recovery of testosterone to > 230 ng/dL (accepted threshold for supplementation) after 12 and 24 months of follow-up [ Time Frame: From the treatment end date to the date when testosterone levels first recovered to > 230 ng/dl within 12 months and 24 months of treatment. ] [ Designated as safety issue: No ]
  • Median time to recovery of testosterone to > 230 ng/dL during the first five years of follow-up [ Time Frame: From the date of ranomization to the post-treatment end date when testosterone levels first recovered to > 230 ng/dl within 5 years after treatment. ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: From the date of randomization to the date of first reported new incidence of any of the above mentioned clinical endpoints. ] [ Designated as safety issue: No ]
  • Rates and cumulative incidence of local/regional progression [ Time Frame: From the date of randomization to the date of the documented presence of local/regional recurrence. ] [ Designated as safety issue: No ]
  • Rates and cumulative incidence of distant metastases [ Time Frame: From the date of randomization to the date of documented distant recurrence. ] [ Designated as safety issue: No ]

Estimated Enrollment: 900
Study Start Date: May 2012
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ADT + GnRH agonist + dose escalated radiation
Patients receive standard androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) 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).
Drug: bicalutamide
Given orally
Drug: buserelin
Given subcutaneously or intramuscularly
Drug: flutamide
Given orally
Drug: goserelin acetate
Given subcutaneously or intramuscularly
Drug: leuprolide acetate
Given subcutaneously or intramuscularly
Drug: triptorelin
Given subcutaneously or intramuscularly
Experimental: ADT + GnRH agonist + dose escalated radiation + TAK-700
Patients receive the same standard ADT with a GnRH agonist and oral antiandrogen. In addition, patients also receive steroid 17alpha-monooxygenase TAK-700 (TAK-700) PO twice daily (BID) for 2 years.
Drug: bicalutamide
Given orally
Drug: buserelin
Given subcutaneously or intramuscularly
Drug: flutamide
Given orally
Drug: goserelin acetate
Given subcutaneously or intramuscularly
Drug: leuprolide acetate
Given subcutaneously or intramuscularly
Drug: orteronel
Given orally
Drug: triptorelin
Given subcutaneously or intramuscularly

  Hide Detailed Description

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 pelvic CT or abdominal and 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/mm^3
  • Platelets ≥ 100,000 cells/mm^3
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01546987

Locations
United States, California
Auburn Radiation Oncology Recruiting
Auburn, California, United States, 95603
Contact: Christopher Jones, MD    916-646-6600      
Radiation Oncology Centers - Cameron Park Recruiting
Cameron Park, California, United States, 95682
Contact: Christopher Jones, MD    916-646-6600      
Mercy Cancer Center at Mercy San Juan Medical Center Recruiting
Carmichael, California, United States, 95608
Contact: Christopher Jones, MD    916-646-6600      
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Howard M. Sandler, MD    734-936-9338      
Radiation Oncology Center - Roseville Recruiting
Roseville, California, United States, 95661
Contact: Christopher Jones, MD    916-646-6600      
Radiological Associates of Sacramento Medical Group, Incorporated Recruiting
Sacramento, California, United States, 95815
Contact: Christopher Jones, MD    916-646-6600      
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi    877-827-3222      
Solano Radiation Oncology Center Recruiting
Vacaville, California, United States, 95687
Contact: Christopher Jones, MD    916-646-6600      
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa Recruiting
Iowa City, Iowa, United States, 52242-1002
Contact: Cancer Information Service    800-237-1225      
United States, Maine
Maine Center for Cancer Medicine and Blood Disorders - Scarborough Recruiting
Scarborough, Maine, United States, 04074
Contact: Ian J. Bristol    207-885-7600      
United States, Maryland
St. Agnes Hospital Cancer Center Recruiting
Baltimore, Maryland, United States, 21229
Contact: Richard S. Hudes, MD    410-368-2965      
United States, Missouri
David C. Pratt Cancer Center at St. John's Mercy Recruiting
Saint Louis, Missouri, United States, 63141
Contact: Clinical Trials Office - David C. Pratt Cancer Center at St. J    314-251-6770      
Missouri Baptist Cancer Center Recruiting
Saint Louis, Missouri, United States, 63131
Contact: Alan P. Lyss, MD    314-996-5514      
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jeff M. Michalski, MD    314-362-8566      
United States, Oklahoma
Natalie Warren Bryant Cancer Center at St. Francis Hospital Recruiting
Tulsa, Oklahoma, United States, 74136
Contact: Charles E. Stewart    918-494-2273      
United States, Pennsylvania
Delaware County Regional Cancer Center at Delaware County Memorial Hospital Recruiting
Drexel Hill, Pennsylvania, United States, 19026
Contact: Rachelle M. Lanciano, MD    610-284-8240      
Adams Cancer Center Recruiting
Gettysburg, Pennsylvania, United States, 17325
Contact: Amit B. Shah    717-741-8180      
Cherry Tree Cancer Center Recruiting
Hanover, Pennsylvania, United States, 17331
Contact: Amit B. Shah    717-741-8180      
York Cancer Center at Apple Hill Medical Center Recruiting
York, Pennsylvania, United States, 17405
Contact: Amit B. Shah    717-741-8180      
United States, South Carolina
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Recruiting
Spartanburg, South Carolina, United States, 29303
Contact: Clinical Trials Office - Gibbs Regional Cancer Center    800-486-5941      
United States, Texas
Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital Recruiting
Fort Worth, Texas, United States, 76104
Contact: Stephen D. Sorgen    817-820-4820      
United States, Utah
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center Recruiting
Murray, Utah, United States, 84157
Contact: R. Jeffrey Lee, MD    801-408-1146      
United States, Wisconsin
St. Mary's Hospital Medical Center - Green Bay Recruiting
Green Bay, Wisconsin, United States, 54303
Contact: Gregory M. Cooley, MD    414-433-8184      
St. Vincent Hospital Regional Cancer Center Recruiting
Green Bay, Wisconsin, United States, 54307-3508
Contact: Clinical Trials Office - St. Vincent Hospital Regional Cancer    920-433-8889      
Gundersen Lutheran Center for Cancer and Blood Recruiting
La Crosse, Wisconsin, United States, 54601
Contact: Clinical Trials Office - Gundersen Lutheran Cancer Center    608-775-2385    cancerctr@gundluth.org   
Bay Area Cancer Care Center at Bay Area Medical Center Recruiting
Marinette, Wisconsin, United States, 54143
Contact: Gregory M. Cooley, MD    414-433-8184      
All Saints Cancer Center at Wheaton Franciscan Healthcare Recruiting
Racine, Wisconsin, United States, 53405
Contact: James H. Taylor, MD    262-687-5000      
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: M. Dror Michaelson, MD, PhD Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01546987     History of Changes
Other Study ID Numbers: RTOG-1115, CDR0000727326, NCI-2012-00700
Study First Received: March 3, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
adenocarcinoma of the prostate
stage I prostate cancer
stage IIA prostate cancer
stage IIB prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Buserelin
Leuprolide
Triptorelin
Flutamide
Goserelin
Bicalutamide
Deslorelin
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 21, 2014