Purpose

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy may stop the adrenal glands from making androgens. Radiation therapy uses high-energy x-rays to kill tumor cells. PURPOSE: This randomized phase III trial studies androgen-deprivation therapy and radiation therapy in treating patients with prostate cancer.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

Criteria


DISEASE CHARACTERISTICS:

- Pathologically (histologically or cytologically) proven diagnosis of prostatic
adenocarcinoma within 180 days of registration at moderate- to high-risk for
recurrence as determined by one of the following combinations:

- Gleason score 7-10 + T1c-T2b (palpation) + prostate-specific antigen (PSA) < 50
ng/mL (includes intermediate- and high-risk patients)

- Gleason score 6 + T2c-T4 (palpation) + PSA < 50 ng/mL OR

- Gleason score 6 + >= 50% (positive) biopsies + PSA < 50 ng/ml

- Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/mL Patients previously
diagnosed with low risk prostate cancer undergoing active surveillance who are
re-biopsied and found to have unfavorable intermediate risk disease or favorable
high risk disease according to the protocol criteria are eligible for enrollment
within 180 days of the repeat biopsy procedure.

- History and/or physical examination (to include at a minimum digital rectal
examination of the prostate and examination of the skeletal system and abdomen) within
90 days prior to registration

- Clinically negative lymph nodes as established by imaging (pelvic and/or abdominal CT
or MR), (but not by 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 ≤ 1.5 cm

- Patients status post a negative lymph node dissection are not eligible

- No evidence of bone metastases (M0) on bone scan within 120 days prior to registration
(Na F PET/CT is an acceptable substitute)

- Equivocal bone scan findings are allowed if plain films (or CT or MRI) are
negative for metastasis

- Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott,
Hybritech) within 120 days prior to registration

- Study entry PSA should not be obtained during the following time frames:

- Ten-day period following prostate biopsy

- Following initiation of hormonal therapy

- Within 30 days after discontinuation of finasteride

- Within 90 days after discontinuation of dutasteride

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-1

- Absolute neutrophil count (ANC) ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin (Hgb) ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0
g/dL is acceptable)

- No prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for
a minimum of 3 years (1,095 days) and not in the pelvis

- E.g., carcinoma in situ of the oral cavity is permissible; however, patients with
prior history of bladder cancer are not allowed

- No prior hematological (e.g., leukemia, lymphoma, or myeloma) malignancy

- No previous radical surgery (prostatectomy) or cryosurgery for prostate cancer

- No previous pelvic irradiation, prostate brachytherapy or bilateral orchiectomy

- No previous hormonal therapy, such as LHRH agonists (e.g., leuprolide, goserelin,
buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens
(e.g., flutamide, bicalutamide, cyproterone acetate), estrogens (e.g., DES), or
surgical castration (orchiectomy)

- Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset
of androgen ablation (both LHRH agonist and oral anti-androgen) is ≤ 45 days prior to
the date of registration.

- No severe, active co-morbidity, defined as any of the following:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of registration

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
or severe liver dysfunction

- Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease
Control (CDC) definition

- Protocol-specific requirements may also exclude immuno-compromised patients

- HIV testing is not required for entry into this protocol

- No patients who are sexually active and not willing/able to use medically acceptable
forms of contraception

- No prior allergic reaction to the hormones involved in this protocol

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior radical surgery (prostatectomy) or cryosurgery for prostate cancer

- No prior pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy

- No prior hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH)
agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist
(e.g., degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone
acetate), estrogens (e.g., diethylstilbestrol (DES) ), or surgical castration
(orchiectomy)

- No prior pharmacologic androgen ablation for prostate cancer unless the onset of
androgen ablation is ≤ 45 days prior to the date of registration

- No finasteride within 30 days prior to registration

- No dutasteride or dutasteride/tamsulosin (Jalyn) within 90 days prior to registration

- No prior or concurrent cytotoxic chemotherapy for prostate cancer

- Prior chemotherapy for a different cancer is allowable

- No prior radiotherapy, including brachytherapy, to the region of the study cancer that
would result in overlap of radiation therapy fields

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Arm I
Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using intensity-modulated radiotherapy (IMRT)* or 3D-conformal radiation therapy (3D-CRT)* once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo permanent prostate implant (PPI) brachytherapy or high-dose rate brachytherapy (I 125 or Pd 103 may be used as the radioisotope).
  • Radiation: radiation therapy
    Undergo RT using IMRT or 3D-CRT
  • Radiation: Whole-pelvic radiotherapy (WPRT)
    Undergo whole-pelvic radiotherapy (WPRT)
Experimental
Arm II
Patients undergo whole-pelvic radiotherapy (WPRT)* (3D-CRT or IMRT) once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo brachytherapy as in arm I.
  • Radiation: Whole-pelvic radiotherapy (WPRT)
    Undergo whole-pelvic radiotherapy (WPRT)

Recruiting Locations

University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
Contact:
Site Public Contact
210-450-3800
phoresearchoffice@uthscsa.edu

More Details

NCT ID
NCT01368588
Status
Recruiting
Sponsor
Radiation Therapy Oncology Group

Study Contact

Detailed Description

OBJECTIVES:

Primary

- Demonstrate that prophylactic, neoadjuvant, androgen-deprivation therapy (NADT) and whole-pelvic radiation therapy (WPRT) will result in improvement in overall survival (OS) of patients with "unfavorable" intermediate-risk or "favorable" high-risk prostate cancer compared to NADT and high-dose prostate (P) and seminal vesicle (SV) radiation therapy (RT) using intensity-modulated RT (IMRT) or external-beam RT (EBRT) with a high-dose rate (HDR) or a permanent prostate (radioactive seed) implant (PPI) boost.

Secondary

- Demonstrate that prophylactic WPRT improves biochemical control.

- Determine the distant metastasis (DM)-free survival.

- Determine the cause-specific survival (CSS).

- Compare acute and late treatment-adverse events between patients receiving NADT and WPRT versus NADT, P, and SV RT.

- Determine whether health-related quality of life (HRQOL), as measured by the Expanded Prostate Cancer Index Composite (EPIC), significantly worsens with increasing aggressiveness of treatment (i.e., Arm 2, NADT + WPRT).

- Determine whether more aggressive treatment (Arm 2, NADT + WPRT) is associated with a greater increase in fatigue (PROMIS Fatigue Short Form) from baseline to last week of treatment, and a greater increase in circulating inflammatory markers (IL-1, IL-1ra, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein).

- Demonstrate an incremental gain in OS and CSS with more aggressive therapy that outweighs any detriments in the primary generic domains of HRQOL (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).

- Determine whether changes in fatigue from baseline to the next three time points (week prior to RT, last week of treatment, and 3 months after treatment) are associated with changes in circulating cytokines, mood, sleep, and daily activities across the same time points.

- Collect paraffin-embedded tissue blocks, plasma, whole blood, and urine for planned and future translational research analyses.

OUTLINE: This is a multicenter study. Patients are stratified according to moderate- to high-risk groups as listed in the Disease Characteristics of this abstract, type of radiotherapy boost (IMRT vs brachytherapy [Low-dose rate (LDR) using PPI or HDR]), and duration of androgen-deprivation therapy (short-term [6 months] vs long-term [32 months]). Patients are randomized to 1 of 2 treatment arms.

All patients receive neoadjuvant androgen-deprivation therapy comprising bicalutamide orally (PO) once daily or flutamide PO thrice daily for 6 months, and luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy comprising leuprolide acetate, goserelin acetate, buserelin, triptorelin, or degarelix subcutaneously (SC) or intramuscularly (IM) every 1 to 3 months beginning 2 months prior to radiotherapy and continuing for 6 or 32 months.

Radiotherapy begins within 8 weeks after beginning LHRH agonist/antagonist injection.

- Arm I: Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using intensity-modulated radiotherapy (IMRT)* or 3D-conformal radiation therapy (3D-CRT)* once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo permanent prostate implant (PPI) brachytherapy or high-dose rate brachytherapy (iodine I 125 or palladium Pd 103 may be used as the radioisotope).

- Arm II: Patients undergo whole-pelvic radiotherapy (WPRT)* (3D-CRT or IMRT) once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo brachytherapy as in arm I.

NOTE: * Patients undergoing brachytherapy implant receive 5 weeks of IMRT, 3D-CRT, or WPRT.

Patients may undergo blood and urine sample collection for correlative studies. Primary tumor tissue samples may also be collected.

Patients may complete the Expanded Prostate Cancer Index Composite (EPIC), the PROMIS-Fatigue Short Form, and the EuroQol (EQ-5D) quality-of-life (QOL) questionnaires at baseline and periodically during treatment. Patients who participate in the QOL portion of the study must also agree to periodic blood collection.

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.