Clinical trial NCT00321698: Radiation Therapy and Docetaxel in Treating Patients Who Are Undergoing Surgery for Localized Prostate Cancer
Official title: Phase I/II Study of Preoperative Radiation and Docetaxel Activity in High Risk Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
First posted: 2006-05-04
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: INCLUSION CRITERIA; 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
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* White blood cell (WBC) \> 3,000/mm\^3
* Neutrophil count \> 1,500/mm\^3
* Platelet count \> 100,000/mm\^3
* Direct bilirubin normal
* Alanine aminotransferase (ALT) \< 2.0 times upper limit of normal (ULN) (1.5 times ULN if alkaline phosphatase \[AP\] \> 2.5 times ULN)
* Alkaline phosphatase (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

EXCLUSION CRITERIA; 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 5 weeks
measure: Pathologic Response Rate at the Phase II Dose
timeFrame: 4-6 weeks after study treatment
Secondary outcomes:
measure: Prostate-specific Antigen Short-term Response Rate Measured as a Percentage Change in PSA
timeFrame: Baseline (pre-treatment) and 1 month after surgery (post-treatment)
measure: Long-term Safety
timeFrame: Regular intervals both study-related and clinical standard of care-related; assessed at end of study treatment. Average timeframe to follow safety was 1 year and includes all grade 3-4 adverse events
measure: Clinical Response to Treatment as Measured by Urologic Examination
timeFrame: Each participant was examined 3, 6, 9, 12 months, and annually for an average of 10 years after surgery.
measure: Surgical Margin Status at Time of Prostatectomy (Count of Subjects With Negative Surgical Margins)
timeFrame: 5 weeks
measure: Efficacy Assessed Using Health-Related Quality of Life by Expanded Prostate Cancer Index Composite and Urinary Symptom Scores by American Urological Association's Measures
timeFrame: Baseline and 12 Months Post-Prostatectomy
measure: Clinical Progression-free Rate as Determined by <0.1ng PSA Results
timeFrame: 3, 6, 9, 12 months and annually, up to 5 years
Other outcomes:
Locations:
city: Portland
country: United States
facility: Veterans Affairs Medical Center - Portland
state: Oregon
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Mark Garzotto, MD
role: PRINCIPAL_INVESTIGATOR
References: