Clinical trial NCT00017563: Combination Chemotherapy Followed by Surgery in Treating Patients With Localized Prostate Cancer
Official title: Phase I/II Study of Neoadjuvant Weekly Docetaxel and Mitoxantrone Prior to Prostatectomy in Patients With High Risk Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage II prostate cancer
stage III prostate cancer
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 57
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving chemotherapy before surgery may shrink the tumor so that it can be removed during surgery.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy followed by surgery in treating patients who have localized prostate cancer.

Detailed description: OBJECTIVES:

* Determine the 5-year freedom from prostate-specific antigen (PSA) recurrence in patients treated with this regimen.
* Define the maximum tolerated dose of neoadjuvant docetaxel and mitoxantrone followed by prostatectomy in patients with high-risk localized prostate cancer. (Phase I completed as of 2/15/02)
* Determine the toxicity of this regimen in these patients.
* Determine the PSA response rate and pathologic response rate in patients treated with this regimen.
* Determine the clinical response in patients treated with this regimen.
* Determine the overall survival of patients treated with this regimen.
* Determine the surgical margin status at time of prostatectomy in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of mitoxantrone. (Phase I completed as of 2/15/02)

Patients receive neoadjuvant docetaxel and mitoxantrone weekly on weeks 1-3. Treatment repeats once a week for a total of 4 courses.

Patients receive escalating doses of mitoxantrone until the maximum tolerated dose is determined. (Phase I completed as of 2/15/02)

Patients undergo prostatectomy 2-4 weeks after completion of neoadjuvant chemotherapy.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the prostate

  * High-risk, as defined by 1 of the following:

    * Stage T2b (palpable bilateral involvement) or surgically resectable T3
    * PSA 15 ng/mL or greater
    * Gleason grade greater than 4+3 (4+3, 4+4, or 5+any, but not 3+4)
* At least a 50% chance of prostate cancer recurrence within 5 years
* Planned prostatectomy as primary therapy
* No evidence of bone metastases by bone scan
* No evidence of lymph nodes greater than 2 cm on pelvic computed tomography (CT) scan (scan required only if PSA greater than 40 ng/mL)

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Eastern Cooperative Oncology Group(ECOG) 0-2

Life expectancy:

* At least 10 years

Hematopoietic:

* White Blood Cell(WBC) at least 3,000/mm\^3
* Neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Conjugated bilirubin no greater than upper limit of normal (ULN)
* Alkaline phosphatase no greater than 4 times ULN
* Alanine transaminase(ALT) no greater than 2 times ULN (1.5 times ULN if alkaline phosphatase greater than 2.5 times ULN)

Renal:

* Not specified

Cardiovascular:

* Ejection fraction greater than 50% by Multiple Gated Acquisition(MUGA)scan

Other:

* No other malignancy within the past 5 years except nonmelanoma skin cancer
* No significant active medical illness that would preclude study therapy
* No peripheral neuropathy grade 2 or greater
* No hypersensitivity to drugs formulated with polysorbate-80
* No significant contraindications to corticosteroids

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior cytotoxic chemotherapy
* No other concurrent cytotoxic chemotherapy

Endocrine therapy:

* No prior or concurrent conventional hormonal therapy

Radiotherapy:

* No prior or concurrent radiotherapy (external beam or brachytherapy)

Surgery:

* See Disease Characteristics

Other:

* No prior or concurrent cryotherapy

Primary outcomes:
measure: Number of Participants With 5-year Freedom From Prostate Specific Antigen (PSA) Recurrence.
timeFrame: Every 3 months after surgery for up to 5 years.
Secondary outcomes:
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
city: Portland
country: United States
facility: Portland VA Medical Center
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Tomasz M. Beer, MD
role: STUDY_CHAIR
References: