Clinical trial NCT00321698
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate stage II prostate cancer stage III prostate cancer
Sponsor: OHSU Knight Cancer Institute
Start date: 2006-04-21; Completion date: 2023-08-18
Enrollment: 25 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
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.

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.

Arms: arm 1: Group 1=radiation only; Group 2=Docetaxel IV over 30mins, 10mg/m2; weekly x 5 weeks starting on day one of radiation; Group 3=Docetaxel IV over 30mins, 20mg/m2; weekly x 5 weeks starting on day one of radiation; Group 4=Docetaxel IV over 30mins, 30mg/m2; weekly x 5 weeks starting on day one of radiation

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) arm 2: Phase II with no phase I dose-limiting toxicities=Docetaxel IV over 30mins, 30mg/m2; weekly x 5 weeks starting on day one of radiation

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)
Interventions: intervention 1: Intensity-Modulated Radiation Therapy (IMRT) intervention 2: Docetaxel+IMRT
Intervention descriptions: intervention 1: Group 1=radiation only; All men in all Arms/Groups receive same radiation treatment protocol. External Beam, 45 Gy (1.8 Gy fractions), 5 per week (daily) x 5 weeks (25 fractions) intervention 2: 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: All men receive same radiation treatment protocol. External Beam, 45 Gy (1.8 Gy fractions), 5 per week (daily) x 5 weeks (25 fractions)

Protocol documents: