Hypofractionated Radiation Therapy in Prostate Cancer

May 15, 2020 updated by: Thomas Zilli

Stereotactic Body Radiation Therapy for cT1c - cT3a Prostate Cancer With a Low Risk of Nodal Metastases (≤ 20%, Roach Index): a Novalis Circle Phase II Prospective Randomized Trial

RATIONALE: It is not yet known whether extreme hypofractionation is equally safe and effective than standard radiation therapy in treating prostate cancer.

PURPOSE: This protocol presents a randomised phase II study aiming to investigate the tolerance and disease control of extreme hypofractionated Radiation Therapy for prostate cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This protocol presents a randomised phase II study aiming to investigate the tolerance and disease control of extreme hypofractionated RT for prostate cancer by delivering 5 x 7.25 Gy = 36.25 Gy over two alternative time schedules: either over 9 days (study A), or over 28 days once-a-week, the same week-day (study B).

The total dose and fractionation schedules have been chosen based on the assumption of their isoeffectivity regarding potential late rectal effects to be expected with a maximum equivalent dose of 74 Gy in 2 Gy fractions and assuming an alpha/beta = 3 Gy for the rectum.

In both arms, the prescribed dose per fraction to the urethra and the surrounding transitional zone will be dropped from 7.25 Gy to 6.5 Gy with a simultaneous integrated boost (SIB) technique. A dose of 5 x 6.5 Gy is equivalent to 31 x 2 Gy assuming an alpha/beta = 3 Gy for the urethra and equivalent to 37 x 2 Gy assuming an alpha/beta = 1.5 Gy for microscopic tumour foci in the transitional zone surrounding the urethra. The two treatment regimens chosen will each be the object of a separate phase I-II study covered by the same protocol and performed in parallel by the participating centres. Randomised assignment to either of the two studies will be introduced to avoid selection bias in treatment assignment within each centre.

OBJECTIVES:

Primary

  • To determine the risk of urinary, rectal and sexual acute and late toxicities rates in patients receiving two different time schedules of extreme hypofractionated radiation therapy

    • Secondary

  • To determine the Quality of life (EORTC QLQ-C30, Prostate cancer module EORTC QLQ-PR25) in patients receiving two different time schedules of extreme hypofractionated radiation therapy
  • To determine the rate of local failure
  • To determine in the two study arms the biochemical disease-free survival bDFS rate
  • To determine in the two study arms the metastases-free survival rate
  • To determine in the two study arms the disease-specific survival rate

OUTLINE:

This is a multicenter study.

Patients undergo extreme hypofractionated radiation therapy for prostate cancer by delivering 5 x 7.25 Gy = 36.25 Gy over two alternative time schedules:

Experimental Arm A: Over 9 days. Experimental Arm B: Over 28 days once-a-week, the same week-day. All patients will be followed up for at least 18 months to contribute to the analysis of the main endpoints of the study. With reference to the secondary endpoints, follow-up will be extended to 10 years.

Stopping rule: In order to avoid exposure of patients to a treatment that may be unsafe, acute GI and GU toxicity will be continuously monitored with the purpose of assisting in the decision of possibly interrupt recruitment in case of an alarming frequency.To this purpose, the procedure of Ivanova et al., 2005 will be applied.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
170

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Aalst, Belgium, 9300
        • Onze Lieve Vrouwziekenhuis
  • Finland
      • Turku, Finland
        • University Hospital
  • Israel
      • Ramat Gan, Israel
        • Sheba Medical Center
  • Netherlands
      • Amsterdam, Netherlands
        • VU University Medical Center
  • Portugal
      • Porto, Portugal
        • Portuguese Institut of Oncology
  • Spain
      • Barcelona, Spain
        • Teknon Oncologic Institute
      • Madrid, Spain
        • Hospital Universitario Sanchinarro
  • Switzerland
      • Geneva, Switzerland, 1211
        • University Hospital
  • Turkey
      • Istanbul, Turkey
        • Neolife Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Age: >18
  • WHO performance status ≤ 2
  • Any patient where prophylactic lymph node irradiation is not required, i.e. risk of nodal microscopic involvement ≤ 20% (according to Roach et al (25):

"N+ (in %) = (Gleason score - 6) x 10 + 2/3 PSA at diagnosis)"

  • T-stage: cT1-cT3a.
  • Previous TURP is allowed provided there is at least 8 weeks interval with radiotherapy.

  • Combined hormonal treatment (Neoadjuvant-concomitant androgen deprivation, AD, for 6 months) is mandatory if two or more of the following tumour characteristics are present: ≥cT2c, Gleason 4+3, PSA >10 ng/ml, perineural invasion, and/or >1/3 of positive biopsies. RT shall be delivered between 2 and 3 months (+/- 1 week) after starting AD and according to the following chronologic sequence:

    1. Neoadjuvant AD for 2 months (30 days of bicalutamide 50mg qd, and a 3-month slow-releasing LH-RH analog to be started 15 days after initiating bicalutamide).
    2. Randomization at the end of the neoadjuvant AD period (2 months after starting AD).
    3. Planning RT (to be started within 1 month after randomization (i.e., between the 2nd and 3th month after initiating AD)
  • Concomitant and adjuvant HT for 4 more months (a second 3-month slow-releasing LH-RH analog injection).

Exclusion Criteria:

  • Inability to obtain a written informed consent
  • Patient preference to be treated with one rather than the other treatment arm.
  • WHO performance status > 2
  • cT3b,cT4
  • Gleason score ≥8
  • Clinical N+ on metastases work-up or N+ risk >20% (Roach algorithm)
  • Severe urinary obstructive symptoms (IPSS symptom index >19)
  • Previous TURP less than 8 weeks before radiotherapy
  • Previous prostate surgery other than TURP

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: 9 days
Patients undergo extreme hypofractionated radiation therapy (Intensity modulated radiation therapy, Volumetric modulated arc therapy, Image guided radiation therapy) once a week over 28 days
Radiation: Intensity modulated radiation therapy
Minimize radiation doses to surrounding area
Radiation: Volumetric modulated arc therapy
Highly conformational dose distribution
Radiation: Image guided radiation therapy
Follow target by the use of fiducial markers and ERB
EXPERIMENTAL: 28 days
Patients undergo extreme hypofractionated radiation therapy (Intensity modulated radiation therapy, Volumetric modulated arc therapy, Image guided radiation therapy) other 9 days.
Radiation: Intensity modulated radiation therapy
Minimize radiation doses to surrounding area
Radiation: Volumetric modulated arc therapy
Highly conformational dose distribution
Radiation: Image guided radiation therapy
Follow target by the use of fiducial markers and ERB

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Tolerance to treatment
Time Frame: up to 5 years
Tolerance to treatment (urinary, rectal, sexual): Acute (up to 90 days) and late (up to 5 years) toxicity follow-up according to NCI CTCAE version 3.0
up to 5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
1. Quality of life
Time Frame: 9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years
Quality of life (EORTC QLQ-C30, Prostate cancer module EORTC QLQ-PR25)
9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years
2. Local failure
Time Frame: 9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years
Assessed by digital rectal examination (DRE). MRI or PET-CT with choline or acetate may be a confirmatory option. Biopsy confirmation is required for those patients with exclusive local failures and candidates for local salvage.
9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years
3. Biochemical disease-free survival bDFS
Time Frame: 9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years
Phoenix definition (PSA nadir + 2 ng/ml)
9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years
4. Metastases-free survival
Time Frame: 9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years
Outcomes 3 or 4 - investigations PET-CT choline
9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years
5. Disease-specific survival
Time Frame: 9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years
Alive/dead status, date and cause of death and prostate cancer disease status (outcomes 3/4 and 5).
9 days (Treatment arm A) or 28 days (Treatment arm B), 12 weeks, 6, 12, 18 months and yearly thereafter, up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Thomas Zilli

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Thomas Zilli, Dr, University Hospital, Geneva

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2012

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 20, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 9, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 19, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 11-196

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

No plan to share participant data for now

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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