Hypofractionated Radiation Therapy in Prostate Cancer

This study is currently recruiting participants.
Verified December 2013 by University Hospital, Geneva
Sponsor:
Information provided by (Responsible Party):
Raymond Miralbell, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01764646
First received: December 20, 2012
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Cancer of Prostate TNM Staging cT1c to cT3a
Low Risk of Nodal Metastases (≤ 20%, Roach Index)
Radiation: Intensity modulated radiation therapy
Radiation: Volumetric modulated arc therapy
Radiation: Image guided radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Tolerance to treatment [ Time Frame: up to 90 days ] [ Designated as safety issue: Yes ]
    Tolerance to treatment (urinary, rectal, sexual): Acute toxicity according to NCI CTCAE version 3.0

  • Tolerance to treatment [ Time Frame: up to 5 years ] [ Designated as safety issue: Yes ]
    Tolerance to treatment (urinary, rectal, sexual): Late toxicity according to NCI CTCAE version 3.0


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Quality of life (EORTC QLQ-C30, Prostate cancer module EORTC QLQ-PR25)

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 152
Study Start Date: September 2012
Estimated Study Completion Date: September 2025
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Radiation: Volumetric modulated arc therapy Radiation: Image guided radiation therapy
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 Radiation: Volumetric modulated arc therapy Radiation: Image guided radiation therapy

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01764646

Contacts
Contact: Raymond Miralbell, MD Raymond.Miralbell@hcuge.ch

Locations
Denmark
Rigshospitalet University Hospital Not yet recruiting
Copenhagen, Denmark
Contact: Svend Aage ENGELHOLM, MD.       svend.aage.engelholm@rh.regionh.dk   
Finland
University Hospital Recruiting
Turku, Finland
Contact: Heikki MINN, MD.       Heikki.Minn@tyks.fi   
Israel
Sheba Medical Center Recruiting
Ramat Gan, Israel
Contact: Zvi SYMON, MD.       Symon.Zvi@sheba.health.gov.il   
Assuta Medical Center Not yet recruiting
Tel Aviv, Israel
Contact: Raphael PFEFFER, MD.       raphaelp@assuta.co.il   
Netherlands
VU University Medical Center Recruiting
Amsterdam, Netherlands
Contact: Ann Marie BRUYNZEEL, MD.       AME.Bruynzeel@vumc.nl   
Portugal
Portuguese Institut of Oncology Recruiting
Porto, Portugal
Contact: Angelo OLIVEIRA, MD.       angelomail@portugalmail.pt   
Spain
Teknon Oncologic Institute Recruiting
Barcelona, Spain
Contact: Sandra JORCANI, MD:       sjorcano@cmteknon.com   
Hospital Universitario Sanchinarro Recruiting
Madrid, Spain
Contact: Carmen RUBIO, MD.       crubio@hospitaldemadrid.com   
Switzerland
University Hospital Recruiting
Geneva, Switzerland, 1211
Contact: Raymond MIRALBELL, MD.       Raymond.Miralbell@unige.ch   
Sub-Investigator: Thomas ZILLI         
Turkey
Neolife Medical Center Recruiting
Istanbul, Turkey
Contact: Ufuk ABACIOGLU, MD.       ufuk.abacioglu@neolife.com.tr   
University Hospital Not yet recruiting
Istanbul, Turkey
Contact: Esra SAGLAM, MD.       esrasaglam@gmail.com   
Sponsors and Collaborators
Raymond Miralbell
Investigators
Principal Investigator: Raymond Miralbell, Pr. University Hospital, Geneva
  More Information

No publications provided

Responsible Party: Raymond Miralbell, Pr., University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01764646     History of Changes
Other Study ID Numbers: 11-196
Study First Received: December 20, 2012
Last Updated: December 11, 2013
Health Authority: Switzerland: Ethikkommission
Switzerland: Federal Office of Public Health

Keywords provided by University Hospital, Geneva:
Prostate cancer
Radiation therapy

Additional relevant MeSH terms:
Neoplasm Metastasis
Prostatic Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on April 17, 2014