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Prostate CancerPhase 1/2NCT00321698

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

A Phase 1/2 study testing Intensity-Modulated Radiation Therapy (IMRT) and Docetaxel+IMRT in people with Prostate Cancer, run by OHSU Knight Cancer Institute at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 100 years, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Intensity-Modulated Radiation Therapy (IMRT) and Docetaxel+IMRT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesUnited States
Study dates
21 Apr 2006to 18 Aug 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 28Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Veterans Affairs Medical Center - Portland

    Portland, Oregon, 97207

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239-3098

Other trials in United States

About this study

Official title: Phase I/II Study of Preoperative Radiation and Docetaxel Activity in High Risk Localized Prostate Cancer

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.

Read the 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
Being tested
Intensity-Modulated Radiation Therapy (IMRT), Docetaxel+IMRT
Keywords
adenocarcinoma of the prostate, stage II prostate cancer, stage III prostate cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intensity-Modulated Radiation Therapy (IMRT)Radiation

    Also called Radiation therapy

    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+IMRTDrug

    Also called Chemotherapy with Radiation therapy

    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)

Study groups in NCT00321698
Study groupRoleWhat they receive
Phase I Dose 1-4ExperimentalGroup 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)
Receives: Radiation: Intensity-Modulated Radiation Therapy (IMRT); Drug: Docetaxel+IMRT
Phase II MTD DoseExperimentalPhase 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)
Receives: Drug: Docetaxel+IMRT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 5 weeks

  2. 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.

    Measured: 4-6 weeks after study treatment

Secondary outcomes (6)

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

    All participants were combined for this assessment as pre-specified in the protocol.

    The percentage change for patients were determined from pre- and post- treatment PSA values. The mean percentage change in PSA will be reported.

    PSA will be monitored every 3-6 months during the first 5 years, then annually after surgery for up to 10 years

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

  2. Long-term Safety

    An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.

    Measured: 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

  3. Clinical Response to Treatment as Measured by Urologic Examination

    Biochemical Recurrence is defined as a detectable or rising PSA value after surgery that is 0.2 ng/mL or greater with a second confirmatory level of 0.2 ng/mL or greater.

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

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

    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 M refers to whether the cancer has metastasized. This means that the cancer has spread outside of the primary tumor to other parts of the body.

    Measured: 5 weeks

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

    Mean change in score from Baseline to 12-months pot-op. A single outcome, Health Related Quality of Life (QOL), was specified in the protocol. All 6 score means and confidence intervals are reported here as a single outcome; a separate row for each score.

    AUA Symptom Score is designed to measure lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia or other causes in men. Higher scores indicate more LUTS (scale 0-35). 1-7, mild; 8-19, moderate; 20-35, severe.

    EPIC quality of life instruments is a 32-item self-report questionnaire that measures the QOL of prostate cancer patients. 4 subscales measuring urinary (further consisting of two sub-components, EPIC Urinary Incontinence Score and EPIC Urinary Obstructive/Irritative Score), bowel, sexual and hormonal changes. Scores for each of the subscales, as well as for each sub-component within the Urinary sub scale, are transformed linearly to a 0-100 scale with higher scores representing better QOL.

    Measured: Baseline and 12 Months Post-Prostatectomy

  6. Clinical Progression-free Rate as Determined by <0.1ng PSA Results

    The estimated percentage of participants who were progression-free at 5 years per analyses of PSA results post-study treatment.

    Measured: 3, 6, 9, 12 months and annually, up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2006 (estimated)
  2. Study start21 Apr 2006
  3. Primary completion1 Oct 2009
  4. Study completion18 Aug 2023

Why it stopped: Funding withdrawal

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00321698
Sponsor's protocol ID
IRB00001581
Other IDs
IIT16179, OHSU-1581, PVAMC-11-1205/ M1675, OHSU-SOL-05077-L, CDR0000467219, NCI-2012-01122
Status last verified
Aug 2024
First submitted
2 May 2006
Last updated
29 Aug 2024
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 39473059

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Intensity-Modulated Radiation Therapy (IMRT) and Docetaxel+IMRT in people with Prostate Cancer, run by OHSU Knight Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: 5 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00321698, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2024.

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