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

NCT00321698 | Terminated Phase 1 Results DMC

• 7 other identifiers: IRB00001581IIT16179OHSU-1581PVAMC-11-1205/ M1675OHSU-SOL-05077-LCDR0000467219NCI-2012-01122
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; stage II prostate cancer; stage III prostate cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  Maximal tolerated dose (MTD) of the combination radiation (45 Gy) and docetaxel. The dose of radiation will be fixed at 45 Gy while the dose of docetaxel will be escalated. The starting dose of docetaxel will be 10 mg/m2 and will be escalated in increments of 10 mg/m2 up to a dose of 30 mg/m2 the pre-planned ceiling). MTD will be the dose that is associated with no more than 1 dose limiting toxicity (DLT) up to 6 patients. The DLT will be defined as clinically significant grade 3 non-hematologic or grade 4 hematologic toxicity, attributable to the chemoirradiation. If 2 of 3 patients experience a DLT, dose escalation will stop and the previous dose level will be considered the MTD. If 1 of 3 has DLT, additional 3 patients will be enrolled at the same dose level. If none of the additional 3 patients has DLT, the dose escalation will continue. If 1 additional patient has DLT, the previous dose will be considered the MTD and dose escalation will be stopped.

  5 weeks

• Pathologic Response Rate at the Phase II Dose

  Pathologic response rate is determined post-prostatectomy by pathologist laboratory analyses. The TNM system is the most widely used cancer staging system. Most hospitals and medical centers use the TNM system as their main method for cancer reporting. In the TNM system: The T refers to the size and extent of the main/primary tumor. T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.

  4-6 weeks after study treatment

Secondary Outcomes (6)

• Prostate-specific Antigen Short-term Response Rate Measured as a Percentage Change in PSA

  Baseline (pre-treatment) and 1 month after surgery (post-treatment)

• Long-term Safety

  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

• Clinical Response to Treatment as Measured by Urologic Examination

  Each participant was examined 3, 6, 9, 12 months, and annually for an average of 10 years after surgery.

• Surgical Margin Status at Time of Prostatectomy (Count of Subjects With Negative Surgical Margins)

  5 weeks

• Efficacy Assessed Using Health-Related Quality of Life by Expanded Prostate Cancer Index Composite and Urinary Symptom Scores by American Urological Association's Measures

  Baseline and 12 Months Post-Prostatectomy

Study Arms (2)

Phase I Dose 1-4

EXPERIMENTAL

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)

Radiation: Intensity-Modulated Radiation Therapy (IMRT); Drug: Docetaxel+IMRT

Phase II MTD Dose

EXPERIMENTAL

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)

Drug: Docetaxel+IMRT

Interventions

Intensity-Modulated Radiation Therapy (IMRT) 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)

Also known as: Radiation therapy

Phase I Dose 1-4

Docetaxel+IMRT 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)

Also known as: Chemotherapy with Radiation therapy

Phase I Dose 1-4; Phase II MTD Dose

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead

Study Sites (2)

Veterans Affairs Medical Center - Portland

Portland, Oregon, 97207, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239-3098, United States

Location

Related Publications (1)

• 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.

  PMID: 39473059 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiotherapy, Intensity-Modulated; Radiotherapy; Drug Therapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Therapeutics

Limitations and Caveats

Patient accrual was not completed due to the sponsor withdrawing funding.

Results Point of Contact

• Title: Dr. Mark Garzotto
• Organization: Portland VAMC

garzotto@ohsu.edu

541-728-0665

Study Officials

• Mark Garzotto, MD

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 2, 2006
• First Posted: May 4, 2006
• Study Start: April 21, 2006
• Primary Completion: October 1, 2009
• Study Completion: August 18, 2023
• Last Updated: August 29, 2024
• Results First Posted: December 30, 2016

Record last verified: 2024-08

Locations

US (2)