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

NCT ID: NCT00321698

Last Updated: 2024-08-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-21
• Study Completion Date: 2023-08-18

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I Dose 1-4

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)

Group Type: EXPERIMENTAL

Intensity-Modulated Radiation Therapy (IMRT)

Intervention Type: RADIATION

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)

Docetaxel+IMRT

Intervention Type: DRUG

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)

Phase II MTD Dose

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)

Group Type: EXPERIMENTAL

Docetaxel+IMRT

Intervention Type: DRUG

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)

Interventions

Intensity-Modulated Radiation Therapy (IMRT)

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 Type: RADIATION

Docetaxel+IMRT

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)

Intervention Type: DRUG

Other Intervention Names

Radiation therapy; Chemotherapy with Radiation therapy

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Mark Garzotto, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Garzotto, MD

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Locations

Veterans Affairs Medical Center - Portland

Portland, Oregon, United States

OHSU Knight Cancer Institute

Portland, Oregon, United States

Countries

United States

References

Ohaegbulam KC, Post CM, Farris PE, Garzotto M, Beer TM, Hung A, Williamson CW. Safety and Efficacy of Neoadjuvant Docetaxel and Radiotherapy in Localized High-Risk Prostate Cancer: Results From a Prospective Pilot Study. Am J Clin Oncol. 2025 Feb 1;48(2):75-82. doi: 10.1097/COC.0000000000001151. Epub 2024 Oct 30.

Reference Type: DERIVED

PMID: 39473059 (View on PubMed)

Other Identifiers

IIT16179

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

OHSU-1581

Identifier Type: OTHER

Identifier Source: secondary_id

PVAMC-11-1205/ M1675

Identifier Type: OTHER

Identifier Source: secondary_id

OHSU-SOL-05077-L

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000467219

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2012-01122

Identifier Type: REGISTRY

Identifier Source: secondary_id

IRB00001581

Identifier Type: -

Identifier Source: org_study_id