Radiation Therapy and Docetaxel in Treating Patients Who Are Undergoing Surgery for Localized Prostate Cancer
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Purpose
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving radiation therapy together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase I/II trial is studying the side effects and best dose of docetaxel when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for high-risk localized prostate cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Prostate Cancer |
Drug: docetaxel Radiation: radiation therapy |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I/II Study of Preoperative Radiation and Docetaxel Activity in High Risk Localized Prostate Cancer |
- Maximum tolerated dose [ Time Frame: Between treatment groups ] [ Designated as safety issue: Yes ]
- Pathologic response rate at the phase II dose [ Time Frame: End of treatment ] [ Designated as safety issue: No ]
- Prostate-specific antigen short-term response rate [ Time Frame: Regular intervals ] [ Designated as safety issue: No ]
- Long-term safety [ Time Frame: Regular intervals ] [ Designated as safety issue: Yes ]
- Clinical response to treatment as measured by urologic examination [ Time Frame: Regular intervals ] [ Designated as safety issue: No ]
- Surgical margin status at time of prostatectomy [ Time Frame: End of treatment ] [ Designated as safety issue: No ]
- Efficacy assessed using Health-Related Quality of Life by Expanded Prostate Cancer Index Composite and urinary symptom scores by American Urological Association's measures [ Time Frame: Regular intervals ] [ Designated as safety issue: No ]
- Clinical progression-free rate [ Time Frame: Regular intervals ] [ Designated as safety issue: No ]
- Response by assessing biologic markers in tissue and serum before treatment [ Time Frame: Data analysis ] [ Designated as safety issue: No ]
- Correlative serum biomarkers following study completion [ Time Frame: Data analysis ] [ Designated as safety issue: No ]
- Molecular impact by RNA content (gene expression profile) compared before and after treatment [ Time Frame: Data analysis ] [ Designated as safety issue: No ]
| Enrollment: | 25 |
| Study Start Date: | January 2006 |
| Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Docetaxel and Radiation
Drug: docetaxel 4 groups of men in phase I study. Group 1=radiation only; Group 2=IV over 30mins, 10mg/m2; weekly x 5 weeks starting on day one of radiation; Group 3=IV over 30mins, 20mg/m2; weekly x 5 weeks starting on day one of radiation; Group 4=IV over 30mins, 30mg/m2; weekly x 5 weeks starting on day one of radiation Phase II with no phase I dose-limiting toxicities=IV over 30mins, 30mg/m2; weekly x 5 weeks starting on day one of radiation Radiation: radiation therapy All men receive same radiation treatment protocol. External Beam, 45 Gy (1.8 Gy fractions), 5 per week (daily) x 5 weeks (25 fractions) |
Drug: docetaxel
4 groups of men in phase I study. Group 1=radiation only; Group 2=IV over 30mins, 10mg/m2; weekly x 5 weeks starting on day one of radiation; Group 3=IV over 30mins, 20mg/m2; weekly x 5 weeks starting on day one of radiation; Group 4=IV over 30mins, 30mg/m2; weekly x 5 weeks starting on day one of radiation Phase II with no phase I dose-limiting toxicities=IV over 30mins, 30mg/m2; weekly x 5 weeks starting on day one of radiation All men receive same radiation treatment protocol. External Beam, 45 Gy (1.8 Gy fractions), 5 per week (daily) x 5 weeks (25 fractions)
|
Detailed Description:
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of neoadjuvant radiotherapy and docetaxel in patients who are undergoing prostatectomy for high-risk localized prostate cancer.
- Determine the pathologic response rate in patients treated at the phase II dose.
Secondary
- Determine the prostate-specific antigen (PSA) short-term response rate in patients treated with this regimen.
- Determine the long-term safety of this regimen prior to radical prostatectomy in these patients.
- Determine the clinical response to this regimen by urologic examination of these patients.
- Determine the surgical margin status at the time of prostatectomy in patients treated with this regimen.
- Determine the effect of this regimen, in terms of Health-Related Quality of Life by Expanded Prostate Cancer Index Composite (EPIC) and urinary symptom scores by the American Urological Association's measures, in these patients.
- Determine the clinical progression-free rate in patients treated with this regimen.
- Identify pretreatment predictors of response in these patients by examining tissue biomarkers in preserved pretreatment biopsy specimens.
- Determine the biologic impact of this regimen on these patients by examining the prostatectomy specimens.
- Collect frozen serum for future analysis of correlative biomarkers.
- Compare the RNA content (gene expression profile) of pre- and post-treatment tumor specimens in order to describe the molecular impact of this regimen on prostate cancer.
OUTLINE: This is a phase I, dose-escalation study of docetaxel followed by a phase II study. All patients undergo a biopsy of the prostate to gather research-only specimens prior to the beginning of treatment.
- Phase I: Patients undergo radiotherapy once daily, 5 days a week, for 5 weeks. Patients also receive docetaxel IV on days 1, 8, 15, 22, and 29. Treatment continues in the absence of disease progression or unacceptable toxicity. Approximately 4-6 weeks after completion of chemoradiotherapy, patients undergo a radical prostatectomy.
Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity. At least 6 patients are treated at the MTD.
- Phase II: Patients undergo radiotherapy as in phase I. Patients also receive docetaxel at the MTD determined in phase I and then undergo prostatectomy as in phase I.
PROJECTED ACCRUAL: A total of 42 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 |
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the prostate
Localized disease, meeting 1 of the following staging criteria:
- Clinical stage T2b (palpable bilateral movement) disease
- Surgically resectable T3 disease
Meets any of the following high-risk* features:
- PSA ≥ 15 ng/mL
- Gleason grade ≥ 4+3 (4+3, 4+4, or 5+any, but not 3+4) NOTE: *High risk defined as > 50% chance of failure with local therapy
- Plans to undergo prostatectomy as primary therapy
No evidence of lymph nodes ≥ 2 cm in diameter by pelvic CT scan
- Scan only required in patients with a PSA ≥ 40 ng/mL
- No evidence of bone metastases by bone scan
PATIENT CHARACTERISTICS:
- Life expectancy ≥ 10 years
- ECOG performance status 0-2
- WBC > 3,000/mm^3
- Neutrophil count > 1,500/mm^3
- Platelet count > 100,000/mm^3
- Direct bilirubin normal
- ALT < 2.0 times upper limit of normal (ULN) (1.5 times ULN if alkaline phosphatase [AP] > 2.5 times ULN)
- AP < 4.0 times ULN
- No other serious medical condition that would preclude study treatment
- No other malignancy within the past 5 years except nonmelanoma skin cancer
- No peripheral neuropathy ≥ grade 2
- No hypersensitivity to drugs formulated with polysorbate 80
- No significant contraindications to corticosteroids
- No history of scleroderma
No active inflammatory bowel disease (IBD) or IBD that is being medically treated
- Inclusion of patients with a remote history of IBD is at the discretion of radiotherapist
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
No prior therapy for prostate cancer, including any of the following:
- Conventional hormonal therapy (e.g., orchiectomy, luteinizing hormone-releasing hormone therapy, antiandrogen therapy, or estrogen therapy)
- External-beam radiotherapy or brachytherapy
- Cryotherapy
- Cytotoxic chemotherapy
- No prior pelvic radiotherapy
Contacts and Locations| United States, Oregon | |
| OHSU Knight Cancer Institute | |
| Portland, Oregon, United States, 97239-3098 | |
| Veterans Affairs Medical Center - Portland | |
| Portland, Oregon, United States, 97207 | |
| Principal Investigator: | Mark Garzotto, MD | OHSU Knight Cancer Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | OHSU Knight Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT00321698 History of Changes |
| Other Study ID Numbers: | CDR0000467219, IIT16179, OHSU-1581, PVAMC-11-1205/ M1675, OHSU-SOL-05077-L |
| Study First Received: | May 2, 2006 |
| Last Updated: | April 30, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by 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 Genital Diseases, Male |
Prostatic Diseases Docetaxel Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 16, 2013