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Androgen Deprivation Therapy and High Dose Radiotherapy With or Without Whole-Pelvic Radiotherapy in Unfavorable Intermediate or Favorable High Risk Prostate Cancer: A Phase III Randomized Trial


Phase 3
18 Years
N/A
Open (Enrolling)
Male
Prostate Cancer

Thank you

Trial Information

Androgen Deprivation Therapy and High Dose Radiotherapy With or Without Whole-Pelvic Radiotherapy in Unfavorable Intermediate or Favorable High Risk Prostate Cancer: A Phase III Randomized Trial


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, 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 [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.

Inclusion 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) or > 50% (positive) biopsies + PSA < 50
ng/mL

- Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/mL

- 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

- 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 12 weeks (90 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

- 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 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 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival of patients treated with NADT and RT vs NADT and WPRT

Safety Issue:

No

Principal Investigator

Mack Roach, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Francisco

Authority:

Unspecified

Study ID:

CDR0000701128

NCT ID:

NCT01368588

Start Date:

July 2011

Completion Date:

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • stage I prostate cancer
  • stage IIA prostate cancer
  • stage IIB prostate cancer
  • stage III prostate cancer
  • Prostatic Neoplasms

Name

Location

CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - MeritCare HospitalFargo, North Dakota  58122
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
Veterans Affairs Medical Center - Long BeachLong Beach, California  90822
Northwest Community HospitalArlington Heights, Illinois  60005
Cape Cod HospitalHyannis, Massachusetts  02601
New York Methodist HospitalBrooklyn, New York  11215-3609
CCOP - GreenvilleGreenville, South Carolina  29615
University of Texas Medical BranchGalveston, Texas  77555-1329
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
CCOP - Virginia Mason Research CenterSeattle, Washington  98101
Utah Valley Regional Medical Center - ProvoProvo, Utah  84604
Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical CenterMilwaukee, Wisconsin  53201-2901
University of California Davis Cancer CenterSacramento, California  95817
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
Hulston Cancer Center at Cox Medical Center SouthSpringfield, Missouri  65807
McDowell Cancer Center at Akron General Medical CenterAkron, Ohio  44307
Lake/University Ireland Cancer CenterMentor, Ohio  44060
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
McKee Medical CenterLoveland, Colorado  80539
Baptist Cancer Institute - JacksonvilleJacksonville, Florida  32207
Adena Regional Medical CenterChillicothe, Ohio  54601
Utah Cancer Specialists at UCS Cancer CenterSalt Lake City, Utah  84106
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos Angeles, California  90048-1865
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
Butterworth Hospital at Spectrum HealthGrand Rapids, Michigan  49503-2560
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Rosenfeld Cancer Center at Abington Memorial HospitalAbington, Pennsylvania  19001
Fox Chase Cancer Center - PhiladelphiaPhiladelphia, Pennsylvania  19111-2497
Kaiser Permanente Medical Center - RosevilleRoseville, California  95661
Kaiser Permanente Medical Center - South San FranciscoSouth San Francisco, California  94080
Ella Milbank Foshay Cancer Center at Jupiter Medical CenterJupiter, Florida  33458
Piedmont HospitalAtlanta, Georgia  30309
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Mary Bird Perkins Cancer Center - Baton RougeBaton Rouge, Louisiana  70809
Hickman Cancer Center at Bixby Medical CenterAdrian, Michigan  49221
Forsyth Regional Cancer Center at Forsyth Medical CenterWinston-Salem, North Carolina  27103
Providence Cancer Center at Providence Portland Medical CenterPortland, Oregon  97213-2967
Providence St. Vincent Medical CenterPortland, Oregon  97225
Dixie Regional Medical Center - East CampusSaint George, Utah  84770
North Star Lodge Cancer Center at Yakima Valley Memorial HospitalYakima, Washington  98902
Regional Cancer Center at Singing River HospitalPascagoula, Mississippi  39581
Cancer Treatment CenterWooster, Ohio  44691
West Allis Memorial HospitalWest Allis, Wisconsin  53227
John B. Amos Cancer CenterColumbus, Georgia  31904
McFarland Clinic, PCAmes, Iowa  50010
Cotton-O'Neil Cancer CenterTopeka, Kansas  66606
St. Mary Mercy HospitalLivonia, Michigan  48154
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Frederick R. and Betty M. Smith Cancer Treatment CenterSparta, New Jersey  07871
Summa Center for Cancer Care at Akron City HospitalAkron, Ohio  44309-2090
Barberton Citizens HospitalBarberton, Ohio  44203
Flower Hospital Cancer CenterSylvania, Ohio  43560
St. Anne Mercy HospitalToledo, Ohio  43623
Penn State Hershey Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
York Cancer Center at Apple Hill Medical CenterYork, Pennsylvania  17405
Jon and Karen Huntsman Cancer Center at Intermountain Medical CenterMurray, Utah  84157
Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical CenterGreen Bay, Wisconsin  54311
Vince Lombardi Cancer Clinic - SheboyganSheboygan, Wisconsin  53081
Aurora Medical CenterSummit, Wisconsin  53066
FirstHealth Moore Regional Community Hospital Comprehensive Cancer CenterPinehurst, North Carolina  28374
St. Vincent's Medical CenterBridgeport, Connecticut  06606
Queen's Cancer Institute at Queen's Medical CenterHonolulu, Hawaii  96813
Lowell General HospitalLowell, Massachusetts  01854
Dubs Cancer Center at Rogue Valley Medical CenterMedford, Oregon  97504
Gibbs Regional Cancer Center at Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Theda Care Cancer InstituteAppleton, Wisconsin  54911
Duke Cancer InstituteDurham, North Carolina  27710
Cancer Institute at St. John's HospitalSpringfield, Illinois  62701
Sentara Cancer Institute at Sentara Norfolk General HospitalNorfolk, Virginia  23507
Providence Cancer CenterAnchorage, Alaska  99508
Lacks Cancer Center at Saint Mary's Health CareGrand Rapids, Michigan  49503
Baptist Medical Center SouthJascksonville, Florida  32258
Florida Cancer Center - PalatkaPalatka, Florida  32177
Memorial Medical CenterModesto, California  95355
United States Air Force Medical Center - Wright-PattersonWright-Patterson AFB, Ohio  45433-5529
Franciscan Skemp Healthcare - La Crosse CampusLa Crosse, Wisconsin  54601
Fountain Valley, California  92708
Cancer Care Center, IncorporatedSalem, Ohio  44460
Providence Cancer Center at PMCCMedford, Oregon  97504
Veterans Affairs Medical Center - MilwaukeeMilwaukee, Wisconsin  53295
Albert Lea Cancer Center at Albert Lea Medical CenterAlbert Lea, Minnesota  56007
Central Maryland Oncology CenterColumbia, Maryland  21044
Hudner Oncology Center at Saint Anne's Hospital - Fall RiverFall River, Massachusetts  02721
Immanuel St. Joseph'sMankato, Minnesota  56002
Luther Midlelfort HospitalEau Claire, Wisconsin  54702
Columbia Saint Mary's Hospital - OzaukeeMequon, Wisconsin  53097
Columbia-Saint Mary's Cancer Care CenterMilwaukee, Wisconsin  53211
Emory Crawford Long HospitalAtlanta, Georgia  30308
Santa Clara Valley Medical CenterSan Jose, California  95128
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Rohnert Park Cancer CenterRohnert Park, California  94928
South Sacramento Cancer CenterSacramento, California  95823
St. Agnes Hospital Cancer CenterBaltimore, Maryland  21229
Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. PetersSaint Peters, Missouri  63376
Renown Institute for Cancer at Renown Regional Medical CenterReno, Nevada  89502
Coleman Radiation Oncology Center at Carter General HospitalMorehead City, North Carolina  28557
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Coastal Carolina Radiation Oncology CenterWilmington, North Carolina  28401
Norris Cotton Cancer Center - NorthSaint Johnsbury, Vermont  05819
Southwest General Health CenterMiddleburgh Heights, Ohio  44130
UHHS Chagrin Highlands Medical CenterOrange Villager, Ohio  44122
UHHS Westlake Medical CenterWestlaker, Ohio  44145
Kansas City Cancer Centers - SouthwestOverland Park, Kansas  66210
Clackamas Radiation Oncology CenterClackamas, Oregon  97015
North Broward Medical CenterDearfield Beach, Florida  33064-3596
Arizona Center for Cancer Care - PeoriaPeoria, Arizona  85381
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Kansas City Cancer Centers - NorthKansas City, Missouri  64154
Upper Delaware Valley Cancer CenterMilford, Pennsylvania  18337
Rocky Mountain Cancer Centers - AuroraAurora, Colorado  80012
Kansas City Cancer Centers - SouthKansas City, Missouri  64131
Door County Cancer Center at Door County Memorial HospitalSturgeon Bay, Wisconsin  54235-1495
Kansas City Cancer Centers - EastLee's Summit, Missouri  64064
Adams Cancer CenterGettysburg, Pennsylvania  17325
Cherry Tree Cancer CenterHanover, Pennsylvania  17331
Tate Cancer Center at Baltimore Washington Medical CenterGlen Burnie, Maryland  21061
Saint Agnes Cancer Center at Saint Agnes Medical CenterFresno, California  93720
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Zangmeister CenterColumbus, Ohio  43219
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