Clinical trial NCT00392535: Intensity-Modulated Radiation Therapy in Treating Patients With Localized Prostate Cancer
Official title: Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer: CHHIP
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
First posted: 2006-10-26
Enrollment: 3216
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known which schedule of intensity-modulated radiation therapy is more effective in treating patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying the side effects of three schedules of intensity-modulated radiation therapy and compares how well they work in treating patients with localized prostate cancer.

Detailed description: OBJECTIVES:

* Determine the safety and efficacy of conventional vs hypofractionated high-dose intensity-modulated radiotherapy in patients with localized prostate cancer.
* Determine the side effects of these regimens in these patients.
* Determine whether hypofractionated radiotherapy schedules will improve the therapeutic ratio by either improving tumor control or reducing normal tissue side effects.
* Compare acute and late treatment-related gastrointestinal and urological toxicity in these patients.
* Determine different prostate-specific antigen-related endpoints for local failure and distant metastases.
* Extend the database of patients treated to escalated doses with dose-volume histograms (DVHs) of normal tissues at risk and relate these to common toxicity endpoints.
* Develop a model to estimate normal tissue complication probability (NTCP) of rectum and bladder for hypofractionated as well as conventional dose-escalated radiotherapy schedules.

OUTLINE: This is a multicenter, randomized, pilot study. Patients are stratified according to risk of seminal vesicle involvement (low-risk vs moderate-risk or high-risk).

* Hormone therapy: Patients receive androgen-deprivation therapy comprising an injection of luteinizing hormone-releasing hormone (LHRH) agonist once monthly for 3-6 months and oral cyproterone acetate beginning the week before the first LHRH agonist injection and continuing for at least 2 weeks after each LHRH agonist injection. Within one week after the last LHRH agonist injection, patients proceed to radiotherapy.
* Radiotherapy: Patients are randomized to 1 of 3 treatment arms.

  * Arm I: Patients undergo conventional high-dose intensity-modulated radiotherapy (IMRT) in 37 fractions over 7.5 weeks.
  * Arm II: Patients undergo hypofractionated high-dose IMRT in 20 fractions over 4 weeks.
  * Arm III: Patients undergo hypofractionated high-dose IMRT in 19 fractions over 3.8 weeks.

In all arms, treatment continues in the absence of unacceptable toxicity.

Quality of life is assessed periodically during study treatment.

After completion of study treatment, patients are followed periodically for up to 15 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 2,163 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the prostate, meeting the following criteria:

  * Clinical stage T1b-T3a, N0, M0
  * Locally confined disease
  * Previously untreated disease
* Prostate-specific antigen (PSA) ≤ 30 ng/mL
* Estimated risk of seminal vesicle involvement \< 30%

  * Estimated risk of seminal vesicle involvement is defined as PSA + (\[Gleason score - 6\] x 10) (i.e., if Gleason score ≤ 6, then PSA must be ≤ 30 ng/mL; if Gleason score = 7, then PSA must be \< 20 ng/mL; if Gleason score = 8, then PSA must be \< 10 ng/mL; if Gleason score = 9 or 10 patient is ineligible)

PATIENT CHARACTERISTICS:

* WHO performance status 0 or 1
* Life expectancy \> 10 years (5 years for patients with poorly differentiated cancers)
* WBC \> 4,000/mm\^3
* Hemoglobin \> 11g/dL
* Platelet count \> 100,000/mm\^3
* No other active malignancy within the past 5 years except basal cell carcinoma
* No hip prosthesis or fixation that would interfere with standard radiation beam configuration
* No comorbid conditions likely to impact on the advisability of radical radiotherapy (e.g., previous inflammatory bowel disease, previous colorectal surgery, significant bladder instability, or urinary incontinence)

PRIOR CONCURRENT THERAPY:

* No prior pelvic radiotherapy
* No prior radical prostatectomy
* No prior androgen-deprivation therapy
* No concurrent full anticoagulation therapy with warfarin or heparin

Primary outcomes:
measure: Time to biochemical or clinical failure
timeFrame: Defined as the time from randomisation to biochemical failure or prostate cancer recurrence up to 5 years
Secondary outcomes:
measure: Disease-free survival
timeFrame: time from randomisation to any prostate cancer-related event or death from any cause up to 15 years
measure: Overall survival
timeFrame: Time from randomisation to death from any cause up to 15 years
measure: Development of metastases
timeFrame: Time from randomisation to development of metastases up to 15 years
measure: Recommencement of hormonal treatment for disease recurrence
timeFrame: Time from randomisation to recommencement of hormone treatment for disease recurrence up to 15 years
measure: Acute and late side-effects
timeFrame: Peak and week 18 bowel and bladder side-effects
Other outcomes:
Locations:
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: England
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Bury St. Edmunds
country: United Kingdom
facility: West Suffolk Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Eastbourne
country: United Kingdom
facility: Eastbourne District General Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: England
city: Prescot
country: United Kingdom
facility: Whiston Hospital
state: England
city: Preston
country: United Kingdom
facility: Rosemere Cancer Centre at Royal Preston Hospital
state: England
city: Runcorn
country: United Kingdom
facility: Halton Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Southport
country: United Kingdom
facility: Southport and Formby District General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Warrington
country: United Kingdom
facility: Warrington Hospital NHS Trust
state: England
city: Worthing
country: United Kingdom
facility: Worthing Hospital
state: England
city: Belfast
country: United Kingdom
facility: Belfast City Hospital Trust
state: Northern Ireland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: David P. Dearnaley, FRCR
role: STUDY_CHAIR
References:
citation: Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, Graham J, Kirkbride P, Logue J, Malik Z, Money-Kyrle J, O'Sullivan JM, Panades M, Parker C, Patterson H, Scrase C, Staffurth J, Stockdale A, Tremlett J, Bidmead M, Mayles H, Naismith O, South C, Gao A, Cruickshank C, Hassan S, Pugh J, Griffin C, Hall E; CHHiP Investigators. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2016 Aug;17(8):1047-1060. doi: 10.1016/S1470-2045(16)30102-4. Epub 2016 Jun 20.