Intensity-Modulated Radiation Therapy in Treating Patients With Localized Prostate Cancer

• ClinicalTrials.gov Identifier: NCT00392535
• Recruitment Status: Unknown
• First Posted: October 26, 2006
• Last Update Posted: February 27, 2019
• Sponsor: Institute of Cancer Research, United Kingdom
• Information provided by (Responsible Party): Institute of Cancer Research, United Kingdom

Tracking Information

• First Submitted Date: October 25, 2006
• First Posted Date: October 26, 2006
• Last Update Posted Date: February 27, 2019
• Actual Study Start Date: October 18, 2002
• Actual Primary Completion Date: September 8, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 26, 2019)

Time to biochemical or clinical failure [ Time Frame: Defined as the time from randomisation to biochemical failure or prostate cancer recurrence up to 5 years ]

Phoenix consensus guidelines as a PSA concentration greater than nadir plus 2 ng/mL.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: February 26, 2019)

• Disease-free survival [ Time Frame: time from randomisation to any prostate cancer-related event or death from any cause up to 15 years ]
• Overall survival [ Time Frame: Time from randomisation to death from any cause up to 15 years ]
• Development of metastases [ Time Frame: Time from randomisation to development of metastases up to 15 years ]
• Recommencement of hormonal treatment for disease recurrence [ Time Frame: Time from randomisation to recommencement of hormone treatment for disease recurrence up to 15 years ]
• Acute and late side-effects [ Time Frame: Peak and week 18 bowel and bladder side-effects ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• Radiation: conventional radiotherapy 74 Gy delivered in 37 fractions
• Radiation: hypofractionated radiation therapy 60 Gy in 20 fractions
• Radiation: hypofractionated radiation therapy 57 Gy in 19 fractions

Study Arms

• Active Comparator: Control arm
  conventional radiotherapy (74 Gy delivered in 37 fractions over 7·4 weeks)
  Intervention: Radiation: conventional radiotherapy 74 Gy delivered in 37 fractions
• Experimental: Hypofractionated arm 1
  Hypofractionated radiotherapy (60 Gy in 20 fractions over 4 weeks)
  Intervention: Radiation: hypofractionated radiation therapy 60 Gy in 20 fractions
• Experimental: Hypofractionated arm 2
  Hypofractionated radiotherapy (57 Gy in 19 fractions over 3·8 weeks)
  Intervention: Radiation: hypofractionated radiation therapy 57 Gy in 19 fractions

• Publications *: 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. Erratum In: Lancet Oncol. 2016 Aug;17 (8):e321.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: February 26, 2019): 3216
• Original Enrollment: Not Provided
• Estimated Study Completion Date: June 17, 2021
• Actual Primary Completion Date: September 8, 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT00392535
• Other Study ID Numbers: CDR0000510112; ICR-CTSU-CHHIP-2006-10007; ISRCTN97182923; EU-20646
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Institute of Cancer Research, United Kingdom
• Original Responsible Party: Not Provided
• Current Study Sponsor: Institute of Cancer Research, United Kingdom
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: David P. Dearnaley, FRCR; Royal Marsden NHS Foundation Trust

• PRS Account: Institute of Cancer Research, United Kingdom
• Verification Date: February 2019