Androgen Suppression Therapy and Radiation Therapy With or Without Docetaxel in Treating Patients With High-Risk Localized Prostate Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00651326
First received: April 1, 2008
Last updated: December 17, 2012
Last verified: December 2012

April 1, 2008
December 17, 2012
March 2008
Not Provided
Disease-free survival [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00651326 on ClinicalTrials.gov Archive Site
  • Overall survival [ Designated as safety issue: No ]
  • Time to biochemical disease progression [ Designated as safety issue: No ]
  • Time to local disease progression [ Designated as safety issue: No ]
  • Time to distant disease progression [ Designated as safety issue: No ]
  • Time to next anti-cancer therapy [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Degree of prostate-specific antigen (PSA) suppression prior to radiotherapy [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]
  • Adverse events [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Androgen Suppression Therapy and Radiation Therapy With or Without Docetaxel in Treating Patients With High-Risk Localized Prostate Cancer
A Phase III Study of Neoadjuvant Docetaxel and Androgen Suppression Plus Radiation Therapy Versus Androgen Suppression Alone Plus Radiation Therapy for High-Risk Localized Adenocarcinoma of the Prostate (DART)

RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as flutamide, bicalutamide, leuprolide, buserelin, and goserelin, may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving androgen suppression therapy together with radiation therapy is more effective with or without docetaxel in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying androgen suppression therapy, radiation therapy, and docetaxel to see how well they work compared with androgen suppression therapy and radiation therapy in treating patients with high-risk localized prostate cancer.

CLOSURE: This trial closed to further accrual in November 2009. The study endpoints will not be reached.

OBJECTIVES:

Primary

  • To compare disease-free survival rates in patients with high-risk localized adenocarcinoma of the prostate treated with androgen suppression therapy and radiotherapy with vs without docetaxel.

Secondary

  • To compare overall survival.
  • To compare time to biochemical disease progression.
  • To compare time to local disease progression.
  • To compare time to distant disease progression.
  • To compare time to next anticancer therapy.
  • To compare progression-free survival.
  • To compare degree of prostate-specific antigen (PSA) suppression prior to radiotherapy.
  • To compare quality of life (QOL) using EORTC QLQ C30 and EORTC QLQ PR25 questionnaires and a trial-specific checklist.
  • To compare the nature, severity, and frequency of adverse events.

OUTLINE: This is a multicenter study. Patients are stratified according to Gleason score (≤ 7 vs ≥ 8), baseline prostate-specific antigen (PSA) (> 20 ng/mL vs ≤ 20 ng/mL), and participating center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive androgen suppression therapy comprising oral flutamide three times daily or oral bicalutamide once daily for 4 weeks AND leuprolide subcutaneously (SC) or intramuscularly every 1-6 months, buserelin SC every 2 or 3 months, or goserelin SC every 1 or 3 months for 3 years. Patients also receive docetaxel IV over 60 minutes on day 1. Treatment with docetaxel repeats every 21 days for up to 4 courses. Beginning at least 4 weeks after completion of chemotherapy, patients undergo pelvic radiotherapy once daily 5 days a week for up to 8 weeks.
  • Arm II: Patients receive androgen suppression therapy and undergo pelvic radiotherapy as in arm I.

Patients complete quality of life questionnaires at baseline, periodically during treatment, and then every 6 months for 5 years.

After completion of study treatment, patients are followed at 3 and 6 months, every 6 months for 5 years, and then annually thereafter.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: bicalutamide
  • Drug: buserelin
  • Drug: flutamide
  • Drug: goserelin
  • Drug: leuprolide acetate
  • Procedure: neoadjuvant therapy
  • Procedure: quality-of-life assessment
  • Radiation: radiation therapy

    46 Gy in 23 fractions over < 5 weeks.

    Boost:

    24-28 Gy in 12-14 fractions over < 3 weeks

  • Drug: Docetaxel
  • Active Comparator: Antiandrogen; LHRH; Docetaxel, Radiation Therapy
    Antiandrogen (Flutamide or Bicalutamide) LHRH agonist (Eligard) Docetaxel
    Interventions:
    • Drug: bicalutamide
    • Drug: buserelin
    • Drug: flutamide
    • Drug: goserelin
    • Drug: leuprolide acetate
    • Procedure: neoadjuvant therapy
    • Procedure: quality-of-life assessment
    • Radiation: radiation therapy
    • Drug: Docetaxel
  • Active Comparator: Antiandrogen; LHRH; Radiation Therapy
    Antiandrogen (Flutamide or Bicalutamide) LHRH agonist (Eligard)
    Interventions:
    • Drug: bicalutamide
    • Drug: buserelin
    • Drug: flutamide
    • Drug: goserelin
    • Drug: leuprolide acetate
    • Procedure: neoadjuvant therapy
    • Procedure: quality-of-life assessment
    • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
48
January 2011
Not Provided

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the prostate

    • Localized (N0, M0) disease
    • No small cell or transitional cell carcinoma in the biopsy specimen
  • Considered to be at high risk for recurrence based on the presence of at least one of the following adverse prognostic features:

    • T stage ≥ 3a
    • Gleason score ≥ 8
    • Baseline prostate-specific antigen (PSA) > 20 ng/mL
  • Deemed to be an appropriate candidate for chemotherapy, as assessed by a medical oncologist
  • Negative pelvic and para-aortic lymph nodes on CT scan or MRI of the abdomen and pelvis

    • Any lymph node appearing ≥ 1.5 cm on CT scan or MRI must be histologically negative by either needle aspirate or lymph node dissection
  • No metastases by chest x-ray and bone scan

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10.0 g/dL
  • AST and/or ALT ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Total bilirubin normal
  • Serum creatinine ≤ 1.5 times ULN
  • Able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French
  • Fertile patients must use effective contraception
  • No history of other malignancies, except adequately treated nonmelanoma skin cancer or other curatively treated solid tumor with no evidence of disease for > 5 years
  • No serious non-malignant disease resulting in a life expectancy of < 10 years
  • No known hypersensitivity to any study medications
  • No existing peripheral neuropathy ≥ grade 2
  • No bilateral hip replacement prostheses
  • No contraindication to pelvic radiotherapy including, but not limited to, inflammatory bowel disease or severe bladder irritability
  • No medical condition that would contraindicate the study treatment regimen, including severe respiratory insufficiency, uncontrolled diabetes, or severe hypertension
  • No other serious illness or psychiatric or medical condition that would preclude management of the patient according to the study, including active uncontrolled infection or significant cardiac dysfunction

PRIOR CONCURRENT THERAPY:

  • Prior androgen suppression therapy allowed provided it was initiated no more than 4 weeks prior to study entry
  • At least 4 weeks since prior 5-alpha-reductase inhibitors (e.g., finasteride) for benign prostatic hypertrophy
  • No prior cytotoxic anticancer therapy
  • No prior chemotherapy for carcinoma of the prostate
  • No prior surgical treatment for carcinoma of the prostate, except transurethral resection or bilateral orchiectomy
  • No prior pelvic radiotherapy
  • No concurrent nilutamide
  • No other concurrent investigational drugs
  • No other concurrent anticancer therapy (cytotoxic therapy, biologic/immunotherapy, or radiotherapy)
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00651326
PR12, CAN-NCIC-PR12, CDR0000589247
Yes
NCIC Clinical Trials Group
NCIC Clinical Trials Group
Not Provided
Study Chair: Michael R. McKenzie, MD, FRCPC British Columbia Cancer Agency
Study Chair: Kim N. Chi, MD British Columbia Cancer Agency
NCIC Clinical Trials Group
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP