Combination Chemotherapy Followed by Surgery in Treating Patients With Localized Prostate Cancer

• ClinicalTrials.gov Identifier: NCT00017563
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Results First Posted: August 31, 2011
• Last Update Posted: April 28, 2017
• Sponsor: OHSU Knight Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Tom Beer, OHSU Knight Cancer Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: docetaxel; Drug: mitoxantrone hydrochloride; Procedure: conventional surgery	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Neoadjuvant Weekly Docetaxel and Mitoxantrone Prior to Prostatectomy in Patients With High Risk Localized Prostate Cancer
• Study Start Date: September 2000
• Actual Primary Completion Date: May 2010

Arms and Interventions

Arm

Intervention/treatment

Experimental: Docetaxel, Mitoxantrone, Conventional Surgery; Drug: Docetaxel-35 mg/m2 i.v. over 15 - 30 minutes will be administered immediately after the mitoxantrone on the same schedule. Drug: Mitoxantrone-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. Procedure/Surgery: Conventional Surgery- Prostatectomy will be scheduled 2-4 weeks after the last dose of chemotherapy

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.; Procedure: conventional surgery; Prostatectomy will be scheduled 2 - 4 weeks after the last dose of chemotherapy.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With 5-year Freedom From Prostate Specific Antigen (PSA) Recurrence. [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Oregon

OHSU Knight Cancer Institute

Portland, Oregon, United States, 97239-3098

Portland VA Medical Center

Portland, Oregon, United States, 97239

Sponsors and Collaborators

OHSU Knight Cancer Institute

National Cancer Institute (NCI)

Investigators

• Study Chair: Tomasz M. Beer, MD; OHSU Knight Cancer Institute

More Information

• Responsible Party: Tom Beer, Principal Investigator, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT00017563
• Other Study ID Numbers: CDR0000068719; OHSU-2794 ( Other Identifier: OHSU IRB ); OHSU-HOR-00037-L; NCI-G01-1962
• First Posted: January 27, 2003
• Results First Posted: August 31, 2011
• Last Update Posted: April 28, 2017
• Last Verified: April 2017

Keywords provided by Tom Beer, OHSU Knight Cancer Institute:

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

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Docetaxel; Mitoxantrone; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors