Androgen Ablation Therapy With or Without Chemotherapy in Treating Patients With Metastatic Prostate Cancer


Prostate Cancer

Trial Phase

Phase 3

Trial Purpose and Description

Trial Purpose

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen ablation therapy may stop the adrenal glands from making androgens. 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 androgen-ablation therapy is more effective with or without docetaxel in treating metastatic prostate cancer.

PURPOSE: This randomized phase III trial is studying androgen-ablation therapy and chemotherapy to see how well they work compared to androgen-ablation therapy alone in treating patients with metastatic prostate cancer.

Trial Description



  • Evaluate the ability of early chemotherapy to improve overall survival of patients commencing androgen deprivation for metastatic prostate cancer.


  • Determine whether early chemotherapy can increase the time to clinical progression (radiographic or symptomatic deterioration due to disease) over hormonal therapy alone.
  • Determine whether early chemotherapy can increase the time to development of hormone-refractory disease over hormonal therapy alone.
  • Determine whether early chemotherapy can increase the time to serological progression over hormonal therapy alone.
  • Determine rates of biochemical response at 6 months and 12 months in the chemohormonal arm versus the hormonal therapy alone arm.
  • Determine the frequency of adverse events and the tolerability of chemotherapy combined with hormonal therapy versus hormonal therapy alone.
  • Determine whether the postulated clinically meaningful increase in disease control is associated with an alteration in overall quality of life using the Functional Assessment of Cancer Therapy-Prostate questionnaire.
  • Determine the ability of prostate-specific antigen changes to be a surrogate for clinical benefit from therapy and overall survival.


  • Determine whether there are proteins differentially translated from the genome in hormone-sensitive prostate cancer, prostate cancer that has responded to hormonal therapy, and hormone-refractory prostate cancer.
  • Determine the frequency of constitutive polymorphisms of enzymes involved in steroid metabolism and other carcinogenic processes.
  • Determine whether the amount and frequency of certain carcinogenic proteins in prostate cancer tissue such as CXCR4 and manganese superoxide dismutase can be correlated with a poor prognosis.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (≥ 70 vs < 70), ECOG performance status (0-1 vs 2), combined androgen blockade for > 30 days (yes vs no), duration of prior adjuvant hormonal therapy (> 12 months vs ≤ 12 months), concurrent bisphosphonate use (yes vs no), and volume of disease (low vs high). Patients are randomized to 1 of 2 treatment arms.

  • Arm A: Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration). Patients also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
  • Arm B: Patients receive androgen-deprivation therapy (as in arm A) alone. Quality of life is assessed at baseline and at weeks 12, 24, 36, and 48.

After completion of study treatment, patients are followed up periodically for up to 10 years.

Participation Guidelines

18 Years - N/A

Eligibility Criteria


- Histologically or cytologically confirmed prostate cancer

- High-volume metastatic disease meeting any of the following criteria:

- Visceral metastases (extranodal)

- Bone metastases

- At least 4 bone lesions

- At least 1 bone lesion must be outside of the vertebral column or

- On androgen-deprivation therapy for < 120 days

- Prostate-specific antigen (PSA) level may not have risen and met criteria for
progression from its lowest point between the start of androgen-deprivation
therapy and randomization


- ECOG performance status (PS) 0-2

- PS 2 eligible only if decline in PS is due to metastatic prostate cancer

- Absolute neutrophil count = 1,500/mm^3

- Platelet count = 100,000/mm^3

- Bilirubin = upper limit of normal (ULN)

- ALT = 2.5 times ULN

- Creatinine clearance = 30 mL/min

- PT and INR = 1.5 times ULN (unless on therapeutic anticoagulation)

- PTT = 1.5 times ULN (unless on therapeutic anticoagulation)

- No prior malignancy in the past 5 years except for basal cell or squamous cell
carcinoma of the skin

- Other malignancies that are considered to have low potential to progress (e.g.,
grade 2, T1a transitional cell carcinoma) may be allowed if approved by study

- No peripheral neuropathy > grade 1

- No history of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80

- No active cardiac disease, including the following:

- Active angina

- Symptomatic congestive heart failure

- Myocardial infarction within the past 6 months

- Fertile patients must use effective contraception


- See Disease Characteristics

- At least 4 weeks since prior major surgery and recovered from all toxicity prior to

- Prior adjuvant or neoadjuvant hormonal therapy allowed provided the following are

- Therapy was discontinued = 12 months ago AND there is no evidence of disease, as
defined by 1 of the following:

- PSA < 0.1 ng/dL after prostatectomy plus hormonal therapy

- PSA < 0.5 ng/dL and has not doubled above nadir after radiotherapy plus
hormonal therapy

- Therapy lasted no more than 24 months

- Last depot injection must have expired by the 24-month mark

- Prior palliative radiotherapy allowed if commenced within 30 days before starting
androgen deprivation

- Anti-androgen therapy allowed as single-agent therapy = 7 days before medial
castration to prevent flare

- No prior chemotherapy in adjuvant or neoadjuvant setting

- No prior hormone therapy in the metastatic setting

- More than 30 days (or 6 half-lives) (whichever is longer) since prior participation
in another clinical trial

- Patients can not simultaneously enroll on CALGB 90202

- Concurrent participation in nontherapeutic trials allowed

- Concurrent antiandrogen therapy (e.g., bicalutamide or flutamide) allowed, but not as
sole hormonal therapy

- No concurrent 5-alpha reductase inhibitors
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
July 2006
Last Updated:
May 15, 2015
Study HIC#:

Clinicaltrials.gov ID: NCT00309985