Radiation Therapy and Docetaxel in Treating Patients Who Are Undergoing Surgery for Localized Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00321698
First received: May 2, 2006
Last updated: April 30, 2013
Last verified: April 2013
  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

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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

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)

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
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
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00321698

Locations
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239-3098
Veterans Affairs Medical Center - Portland
Portland, Oregon, United States, 97207
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
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
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 01, 2014