Hormone Therapy and Radiation Therapy or Hormone Therapy and Radiation Therapy Followed by Docetaxel and Prednisone in Treating Patients With Localized Prostate Cancer

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 3

Conditions: Prostate Cancer

Treatments: Drug: docetaxel; Drug: Oral antiandrogen; Drug: Dexamethasone; Radiation: Radiation therapy; Drug: Prednisone; Drug: LHRH agonist

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00288080

RTOG-0521

NCI-2009-00728 (Registry Identifier)

CDR0000462375

Details and patient eligibility

About

RATIONALE: Androgens can cause the growth of prostate cancer cells. Hormone therapy using drugs, such as leuprolide, goserelin, flutamide, or bicalutamide, may fight prostate cancer by lowering the amount of androgens the body makes. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel and prednisone, 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 hormone therapy and radiation therapy together with chemotherapy is more effective than giving hormone therapy together with radiation therapy in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying hormone therapy and radiation therapy followed by docetaxel and prednisone to see how well it works compared to hormone therapy and radiation therapy in treating patients with localized prostate cancer.

Full description

OBJECTIVES:

Primary

• Compare the relative efficacy, in terms of overall survival, of the combination of androgen suppression and radiotherapy versus androgen suppression and radiotherapy followed by docetaxel and prednisone in patients with localized, high-risk prostate cancer.

Secondary

• Compare the disease-free survival and incidence of adverse events in patients treated with these regimens.
• Compare the biochemical control, local control, and freedom from distant metastases in patients treated with these regimens.
• Determine the validity of prostate-specific antigen (PSA)-defined endpoints as a surrogate for overall survival of patients treated with these regimens.
• Compare the time interval between biochemical failure and distant metastases with respect to testosterone level in patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to risk group.

• Arm I: Patients receive androgen suppression therapy comprising luteinizing hormone-releasing hormone (LHRH) agonist (e.g., leuprolide acetate, goserelin, buserelin, or triptorelin) and oral antiandrogen (i.e., oral flutamide 3 times daily for 2 months or oral bicalutamide once daily for 2 months). Beginning at week 8, patients undergo radiotherapy 5 days a week for approximately 8 weeks. Antiandrogen therapy is discontinued at completion of radiotherapy, but LHRH agonist therapy continues for 20 months.
• Arm II: Patients receive androgen suppression therapy and undergo radiotherapy as in arm I. Beginning 4 weeks after completion of radiotherapy, patients receive docetaxel IV over 1 hour on day 1 and oral prednisone daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients continue LHRH agonist therapy as in arm I.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.

Enrollment: 612 patients

Sex: Male

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer at high-risk for recurrence within the past 180 days as determined by 1 of the following combinations (risk groups):

  • Gleason score ≥ 9, prostate-specific antigen (PSA) ≤ 150 ng/mL, and any T stage
  • Gleason score 8, PSA < 20 ng/mL, and stage ≥ T2
  • Gleason score 8, PSA 20-150 ng/mL, and any T stage
  • Gleason score 7, PSA 20-150 ng/mL, and any T stage

• Clinically negative lymph nodes by imaging (pelvic CT scan or pelvic MRI), nodal sampling, or dissection within 90 days prior to study entry

  • Equivocal or questionable lymph nodes ≤ 1.5 cm by imaging allowed
  • Positive lymph nodes by capromab pendetide (ProstaScint^®) scan with a corresponding lymph node ≤ 1.5 cm by CT scan or MRI allowed

• PSA ≤ 150 ng/mL

  • Cannot have been obtained during any of the following time points:

    • 10-day period after prostate biopsy
    • After initiation of hormonal therapy
    • Within 30 days after discontinuation of finasteride
    • Within 90 days after discontinuation of dutasteride

• No distant metastases by physical exam and bone scan

  • Equivocal bone scan findings allowed if plain films are negative

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Platelet count ≥ 100,000/mm^3
• Absolute neutrophil count ≥ 1,800/mm^3
• Hemoglobin ≥ 8 g/dL (transfusion or other intervention allowed)
• Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• Fertile patients must use effective contraception during and for at least 3 months after completion of study treatment
• No prior invasive malignancy, except nonmelanomatous skin cancer or other malignancy, unless disease-free for ≥ 3 years (e.g., carcinoma in situ of the oral cavity or bladder are allowed)
• No unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
• No transmural myocardial infarction within the past 6 months
• No acute bacterial or fungal infection requiring intravenous antibiotics
• No AIDS
• No prior allergic reaction to any study drugs or other drugs formulated with polysorbate 80
• No existing peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

• At least 60 days since prior 5-alpha reductase inhibitor (e.g., finasteride) for prostatic hypertrophy

• At least 90 days since prior testosterone

• Prior pharmacologic androgen ablation for prostate cancer allowed provided androgen ablation was initiated no more than 50 days prior to study entry

• No prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy

• No prior systemic chemotherapy for prostate cancer

  • Prior chemotherapy for a different cancer is allowed

• No prior radiotherapy, including brachytherapy, to the region of prostate cancer that would result in overlap of radiotherapy fields

• Intensity modulated radiotherapy allowed

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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612 participants in 2 patient groups

Androgen suppression + Radiation Therapy

Active Comparator group

Description:

Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of radiation therapy (RT).

Treatment:

Drug: LHRH agonist

Radiation: Radiation therapy

Drug: Oral antiandrogen

Androgen suppression + Radiation Therapy + Chemotherapy

Experimental group

Description:

Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.

Treatment:

Drug: LHRH agonist

Radiation: Radiation therapy

Drug: docetaxel

Drug: Oral antiandrogen

Drug: Dexamethasone

Drug: Prednisone