Surgery With or Without Docetaxel and Leuprolide or Goserelin in Treating Patients With High-Risk Localized Prostate Cancer - Full Text View

Sponsor:	Cancer and Leukemia Group B
Collaborators:	National Cancer Institute (NCI) Eastern Cooperative Oncology Group NCIC Clinical Trials Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00430183

Purpose

RATIONALE: 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. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as goserelin and leuprolide, may stop the adrenal glands from making androgens. Giving docetaxel and leuprolide or goserelin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether giving docetaxel and leuprolide or goserelin before surgery is more effective than surgery alone in treating patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying docetaxel and leuprolide or goserelin to see how well they work when given before surgery compared with surgery alone in treating patients with high-risk localized prostate cancer.

Condition	Intervention	Phase
Prostate Cancer	Drug: docetaxel Drug: goserelin Drug: leuprolide acetate Procedure: conventional surgery	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Randomized Phase III Study of Neo-Adjuvant Docetaxel and Androgen Deprivation Prior to Radical Prostatectomy Versus Immediate Radical Prostatectomy in Patients With High-Risk, Clinically Localized Prostate Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer Surgery

Drug Information available for: Leuprolide Goserelin Leuprolide acetate Docetaxel

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

3-year biochemical progression-free survival (bPFS) rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

5-year bPFS rate and bPFS [ Designated as safety issue: No ]
Time to clinical local recurrence [ Designated as safety issue: No ]
Time to metastatic disease progression [ Designated as safety issue: No ]
Unacceptable toxicity [ Designated as safety issue: Yes ]
Prostate cancer-specific-free survival [ Designated as safety issue: No ]
Disease progression [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Death [ Designated as safety issue: No ]

Estimated Enrollment:	750
Study Start Date:	December 2006
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive goserelin subcutaneously or leuprolide acetate intramuscularly once every 4 or 12 weeks for 18-24 weeks. They also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 3 weeks for up to 6 courses. Within 60 days after completion of chemohormonal therapy, patients undergo radical prostatectomy with staging pelvic lymphadenectomy.	Drug: docetaxel Given IV over 1 hour Drug: goserelin Given subcutaneously Drug: leuprolide acetate Given intramuscularly Procedure: conventional surgery Patients undergo radical prostatectomy with staging pelvic lymphadenectomy
Arm II: Active Comparator Within 60 days after randomization, patients undergo radical prostatectomy with staging pelvic lymphadenectomy.	Procedure: conventional surgery Patients undergo radical prostatectomy with staging pelvic lymphadenectomy

Detailed Description:

OBJECTIVES:

Primary

Compare the rate of 3-year biochemical progression-free survival (bPFS) in patients with high-risk, clinically localized prostate cancer treated with radical prostatectomy with vs without neoadjuvant chemohormonal therapy comprising docetaxel and androgen-deprivation therapy with leuprolide acetate or goserelin.

Secondary

Compare the 5-year bPFS rate, bPFS, disease progression, disease-free survival, and overall survival of patients treated with these regimens.
Determine the safety and tolerability of neoadjuvant docetaxel and androgen-deprivation therapy in these patients.
Compare the time to clinically apparent local disease recurrence and metastatic disease in patients treated with these regimens.
Compare pathologic tumor stage, frequency of lymph node metastases, and positive margin rates in patients treated with these regimens.
Determine if changes in serum testosterone levels will predict bPFS in these patients.
Determine, prospectively, whether prostate-specific antigen doubling time is a surrogate endpoint for time to clinical metastases and overall survival in these patients.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to nomogram-predicted biochemical progression-free survival at 5 years (0-20.9% vs 21-39.9% vs 40-59.9% vs ≥ 60%) and androgen-deprivation therapy in the past 3 months (no vs yes). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive goserelin subcutaneously or leuprolide acetate intramuscularly once every 4 or 12 weeks for 18-24 weeks. They also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 3 weeks for up to 6 courses. Within 60 days after completion of chemohormonal therapy, patients undergo radical prostatectomy with staging pelvic lymphadenectomy.
Arm II: Within 60 days after randomization, patients undergo radical prostatectomy with staging pelvic lymphadenectomy.

After completion of study therapy, patients are followed at 1 and 3 months and then periodically for up to 15 years.

PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the prostate
- No small cell, neuroendocrine, or transitional cell carcinoma
Clinically localized, stage T1-3a disease
No radiographic evidence of metastatic disease*, as demonstrated by all of the following:
- No lymph nodes > 1 cm by CT scan or MRI of the abdomen and pelvis or endorectal MRI of the pelvis
  - A negative biopsy required for lymph node(s) that measure > 1 cm
    - If > 1 lymph node is > 1 cm, the largest or most accessible node is biopsied
- Negative bone scan with plain films and/or MRI/CT scan confirmation, if necessary NOTE: *Positive positron emission tomography scan and Prostascint scans are not considered proof of metastatic disease
Serum prostate-specific antigen level ≤ 100 ng/mL within the past 6 weeks
Patients must have a known Gleason sum based on biopsy or TURP at study entry
High-risk disease, meeting 1 of the following criteria:
- Probability of biochemical progression-free survival at 5 years after surgery < 60% by Kattan nomogram prediction
- Biopsy Gleason score 8 to 10
Deemed an appropriate candidate for radical prostatectomy

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy > 10 years
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 150,000/mm^3
Creatinine ≤ 2.0 mg/dL
Bilirubin normal (≤ 2.5 times upper limit of normal [ULN] for patients with Gilbert's disease)
AST and ALT ≤ 1.5 times ULN
Fertile patients must use effective contraception during and for ≥ 2 months after completion of study treatment
Not at high risk for cardiac complications
- Prior deep venous thrombosis, pulmonary embolism, and/or cerebrovascular accident allowed

PRIOR CONCURRENT THERAPY:

No prior treatment for prostate cancer, including surgery, pelvic lymph node dissection, radiotherapy, or chemotherapy
- Prior transurethral resection of prostate allowed
Prior androgen-deprivation therapy (e.g., luteinizing hormone-releasing hormone agonists, antiandrogens, or both) lasting ≤ 3 months allowed
Concurrent systemic anticoagulation allowed
No concurrent oral antiandrogens
No concurrent aprepitant
No other concurrent chemotherapeutic agents except for any of the following:
- Steroids given for adrenal failure
- Hormones administered for nondisease-related conditions (e.g., insulin for diabetes)
- Intermittent use of dexamethasone as an antiemetic or as pretreatment for patients receiving docetaxel

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00430183

Show 216 Study Locations

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

NCIC Clinical Trials Group

Investigators

Study Chair:	James A. Eastham, MD	Memorial Sloan-Kettering Cancer Center
Study Chair:	Martin G. Sanda, MD	Beth Israel Deaconess Medical Center
Study Chair:	Martin E. Gleave, MD	Vancouver General Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Cancer and Leukemia Group B ( Richard L. Schilsky )
Study ID Numbers:	CDR0000526353, CALGB-90203
Study First Received:	January 30, 2007
Last Updated:	November 20, 2009
ClinicalTrials.gov Identifier:	NCT00430183 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I prostate cancer
stage II prostate cancer
stage III prostate cancer
adenocarcinoma of the prostate

Additional relevant MeSH terms:

Genital Neoplasms, Male
Prostatic Diseases
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Goserelin
Urogenital Neoplasms
Reproductive Control Agents
Genital Diseases, Male

Pharmacologic Actions
Docetaxel
Neoplasms
Neoplasms by Site
Leuprolide
Fertility Agents, Female
Therapeutic Uses
Fertility Agents
Prostatic Neoplasms

ClinicalTrials.gov processed this record on November 27, 2009