Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage II prostate cancer, stage III prostate cancer
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.
Interventions
DRUGdocetaxel
35 mg/m2 i.v. over 15 - 30 minutes will be administered immediately after the mitoxantrone on the same schedule.
DRUGmitoxantrone hydrochloride
Initial dose will be 2 mg/m2 weekly for 3 of every 4 weeks. The dose will then be escalated as described in the dose escalation section up to a maximum dose of 6 mg/m2 weekly for 3 of every 4 weeks.
PROCEDUREconventional surgery
Prostatectomy will be scheduled 2 - 4 weeks after the last dose of chemotherapy.
Sponsors
National Cancer Institute (NCI)
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 5-year Freedom From Prostate Specific Antigen (PSA) Recurrence. | Every 3 months after surgery for up to 5 years. | Number of participants that experienced 5-year freedom from Prostate Specific Antigen (PSA) recurrence (PSA \> 0.4 ng/ml confirmed by a second PSA that is higher than the first by any amount (2)) in men with high risk localized prostate cancer treated with neoadjuvant docetaxel/mitoxantrone followed by surgery. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel and Mitox Drug: docetaxel
35 mg/m2 i.v. over 15 - 30 minutes will be administered immediately after the mitoxantrone on the same schedule.
Drug: mitoxantrone hydrochloride
Initial dose will be 2 mg/m2 weekly for 3 of every 4 weeks. The dose will then be escalated as described in the dose escalation section up to a maximum dose of 6 mg/m2 weekly for 3 of every 4 weeks. | 57 |
| Total | 57 |
Baseline characteristics
| Characteristic | Docetaxel and Mitox |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 18 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Age, Continuous | 61.56 years STANDARD_DEVIATION 6.279 |
| Region of Enrollment United States | 57 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 57 / 57 |
| serious Total, serious adverse events | 43 / 57 |
Outcome results
Primary
Number of Participants With 5-year Freedom From Prostate Specific Antigen (PSA) Recurrence.
Number of participants that experienced 5-year freedom from Prostate Specific Antigen (PSA) recurrence (PSA \> 0.4 ng/ml confirmed by a second PSA that is higher than the first by any amount (2)) in men with high risk localized prostate cancer treated with neoadjuvant docetaxel/mitoxantrone followed by surgery.
Time frame: Every 3 months after surgery for up to 5 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel and Mitox | Number of Participants With 5-year Freedom From Prostate Specific Antigen (PSA) Recurrence. | 30 participants |