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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Radiation Therapy Oncology Group
Sponsor:
Collaborators:
NRG Oncology Foundation, Inc.
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT01546987
First received: March 3, 2012
Last updated: July 9, 2014
Last verified: July 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

  Show Detailed Description

  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/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/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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01546987

  Show 176 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
NRG Oncology Foundation, Inc.
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: July 9, 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 July 29, 2014