search
Back to results

A Study of Prostate and pelvIs Versus prOsTate Alone Treatment for Locally Advanced Prostate Cancer (PIVOTAL)

Primary Purpose

Prostate Cancer

Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Prostate alone IMRT
Prostate and pelvis IMRT
Sponsored by
Institute of Cancer Research, United Kingdom
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologically confirmed, non-metastatic adenocarcinoma of the prostate, previously untreated (other than by neoadjuvant hormonal treatment)

  2. National Collaborative Cancer Network locally advanced disease (T3b± or T4)43 or:

    • Estimated risk of pelvic lymph node involvement ≥30% * and either:

    • Gleason 9 or 10 or
    • Gleason 8 and one other high risk feature (T3± disease or PSA >20) or
    • Gleason 7 and 2 high risk features (T3± disease and PSA ≥30)
  3. WHO performance status 0 or 1
  4. Normal blood count (Hb > 11g/dl, WBC >4000/mm3, platelets >100,000/mm3)
  5. LHRH analogue therapy for 6-9 months duration prior to proposed radiotherapy treatment and PSA < 4ng/ml prior to randomisation.
  6. Age ≥ 18 years
  7. Patients must be prepared to attend follow up. All patients participating in the Patient Reported Outcomes (PRO) Study must have adequate cognitive ability to complete the PRO questionnaires.

  8. Written informed consent

    • T3a disease should be demonstrated convincingly, either clinically or by MRI. T3b disease (seminal vesicle involvement) must be convincingly demonstrated on MR.

      • Risk of pelvic lymph node involvement = (Gleason score - 6) x 10 + 2/3 PSA

Exclusion criteria:

  1. Prior pelvic radiotherapy
  2. Prior major pelvic surgery (e.g. colectomy, colostomy, cystectomy, prostatectomy)*
  3. Radiologically suspicious (short axis diameter ≥1.0cm unless biopsied and negative) or pathologically confirmed lymph node involvement
  4. Life expectancy < 5 years
  5. Castrate resistant prostate cancer (rising PSA after LHRHa and anti-androgen)
  6. Previous active malignancy within the last 5 years other than basal cell carcinoma
  7. Co-morbid conditions likely to impact on the decision to treat with radiotherapy (e.g. previous inflammatory bowel disease, previous colo-rectal surgery, significant bladder instability or urinary incontinence)

  8. Bilateral hip prosthesis or fixation which would interfere with standard radiation beam configuration

    • Patients who have undergone minor pelvic surgery will be eligible (eg appendicectomy, trans urethral resection of prostate (TURP), exploratory laparoscopy, haemorrhoidectomy, inguinal/femoral hernia repair)

Sites / Locations

  • Queen Elizabeth
  • Addenbrooke's Hospital
  • Velindre Hospital
  • Ipswich
  • Clatterbridge Centre for Oncology
  • Royal Marsden NHSFT
  • Freeman Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Prostate Alone IMRT

Prostate & Pelvis IMRT

Arm Description

Participants will receive standard prostate Intensity Modulated Radiotherapy (IMRT) of 74Gy in 37 fractions delivered over 7.5 weeks.

Participants will receive prostate and pelvis IMRT with a dose of 74Gy in 37 fractions delivered over 7.5 weeks to the prostate and 60Gy in 37 fractions delivered over 7.5weeks to the pelvis.

Outcomes

Primary Outcome Measures

Acute lower GI RTOG toxicity at week 18 of follow-up.
Proportion of patients with acute GI RTOG grade ≥2 toxicity at week 18 from start of radiotherapy calculated as the number of patients with grade ≥2 toxicity at week 18 over the number of evaluable at week 18.

Secondary Outcome Measures

Ability to deliver 60Gy in 37 fractions to the pelvis using the varying radiotherapy planning techniques and delivery systems at the participating centres.
Late (1 and 2 year) toxicity
Measured using RTOG toxicity scale and CTCAE
Patient Reported Outcomes
Participants are requested to complete questionnaires to record the impact of the treatments on bowel and bladder function.
Biochemical progression free survival
Time to local progression
Time to distant metastases
Overall survival

Full Information

First Posted
October 26, 2011
Last Updated
January 2, 2019
Sponsor
Institute of Cancer Research, United Kingdom
Collaborators
Cancer Research UK
search

1. Study Identification

Unique Protocol Identification Number
NCT01685190
Brief Title
A Study of Prostate and pelvIs Versus prOsTate Alone Treatment for Locally Advanced Prostate Cancer
Acronym
PIVOTAL
Official Title
A Randomised Phase II Trial of Prostate and pelvIs Versus prOsTate Alone Treatment for Locally Advanced Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 2011 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Cancer Research, United Kingdom
Collaborators
Cancer Research UK

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Prostate cancer is the most common male cancer in the UK with 35,000 cases diagnosed annually. 35% of these are locally advanced disease. These patients have a high chance of pelvic lymph node involvement and have relatively poor prostate cancer survival rates of 22.5% at 10 years. One of the standard treatments for these patients is radiotherapy to the prostate. PIVOTAL is a multi-centre phase II non-comparative randomised feasibility trial, in which patients with a high chance of pelvic lymph node involvement are randomised between prostate radiotherapy alone and prostate + pelvic radiotherapy. Both groups will receive radiotherapy called Intensity Modulated Radiation Therapy (IMRT). This is a relatively new method of shaping radiotherapy treatment beams which allows the tumour to be treated more precisely, whilst avoiding more of the surrounding normal, healthy tissues (particularly the rectum, bladder and bowel). Using IMRT, it is possible to deliver higher doses of radiotherapy to the pelvis than with previous radiotherapy methods - this has been tested in a single hospital, single group setting and levels of side effects (toxicity) were acceptable. PIVOTAL aims to find out whether toxicity levels at 18 weeks from the start of radiotherapy remain acceptable when treatment is given in multiple cancer centres across the UK. It is randomised to ensure unbiased collection of acute toxicity data and to provide information on patients' willingness to participate in a randomised study. Should the phase II study be successful, the investigators would develop a phase III trial to compare treatment effectiveness (disease control). Patients who enter PIVOTAL will be followed up for two years from the start of radiotherapy and data relating to toxicity will be collected. They will also be asked to complete patient related symptoms questionnaires. Data related to disease recurrence will then be collected annually from patients' standard hospital visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
124 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prostate Alone IMRT
Arm Type
Active Comparator
Arm Description
Participants will receive standard prostate Intensity Modulated Radiotherapy (IMRT) of 74Gy in 37 fractions delivered over 7.5 weeks.
Arm Title
Prostate & Pelvis IMRT
Arm Type
Experimental
Arm Description
Participants will receive prostate and pelvis IMRT with a dose of 74Gy in 37 fractions delivered over 7.5 weeks to the prostate and 60Gy in 37 fractions delivered over 7.5weeks to the pelvis.
Intervention Type
Radiation
Intervention Name(s)
Prostate alone IMRT
Intervention Description
Participants will receive standard prostate IMRT of 74Gy in 37 fractions delivered over 7.5 weeks.
Intervention Type
Radiation
Intervention Name(s)
Prostate and pelvis IMRT
Intervention Description
Participants will receive prostate and pelvis IMRT with a dose of 74Gy in 37 fractions delivered over 7.5 weeks to the prostate and 60Gy in 37 fractions delivered over 7.5weeks to the pelvis.
Primary Outcome Measure Information:
Title
Acute lower GI RTOG toxicity at week 18 of follow-up.
Description
Proportion of patients with acute GI RTOG grade ≥2 toxicity at week 18 from start of radiotherapy calculated as the number of patients with grade ≥2 toxicity at week 18 over the number of evaluable at week 18.
Time Frame
18 weeks post treatment
Secondary Outcome Measure Information:
Title
Ability to deliver 60Gy in 37 fractions to the pelvis using the varying radiotherapy planning techniques and delivery systems at the participating centres.
Time Frame
2 yr
Title
Late (1 and 2 year) toxicity
Description
Measured using RTOG toxicity scale and CTCAE
Time Frame
2 yr
Title
Patient Reported Outcomes
Description
Participants are requested to complete questionnaires to record the impact of the treatments on bowel and bladder function.
Time Frame
2 yr
Title
Biochemical progression free survival
Time Frame
10 yr
Title
Time to local progression
Time Frame
10 yr
Title
Time to distant metastases
Time Frame
10 yr
Title
Overall survival
Time Frame
10 yr

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed, non-metastatic adenocarcinoma of the prostate, previously untreated (other than by neoadjuvant hormonal treatment) National Collaborative Cancer Network locally advanced disease (T3b± or T4)43 or: • Estimated risk of pelvic lymph node involvement ≥30% * and either: Gleason 9 or 10 or Gleason 8 and one other high risk feature (T3± disease or PSA >20) or Gleason 7 and 2 high risk features (T3± disease and PSA ≥30) WHO performance status 0 or 1 Normal blood count (Hb > 11g/dl, WBC >4000/mm3, platelets >100,000/mm3) LHRH analogue therapy for 6-9 months duration prior to proposed radiotherapy treatment and PSA < 4ng/ml prior to randomisation. Age ≥ 18 years Patients must be prepared to attend follow up. All patients participating in the Patient Reported Outcomes (PRO) Study must have adequate cognitive ability to complete the PRO questionnaires. Written informed consent T3a disease should be demonstrated convincingly, either clinically or by MRI. T3b disease (seminal vesicle involvement) must be convincingly demonstrated on MR. Risk of pelvic lymph node involvement = (Gleason score - 6) x 10 + 2/3 PSA Exclusion criteria: Prior pelvic radiotherapy Prior major pelvic surgery (e.g. colectomy, colostomy, cystectomy, prostatectomy)* Radiologically suspicious (short axis diameter ≥1.0cm unless biopsied and negative) or pathologically confirmed lymph node involvement Life expectancy < 5 years Castrate resistant prostate cancer (rising PSA after LHRHa and anti-androgen) Previous active malignancy within the last 5 years other than basal cell carcinoma Co-morbid conditions likely to impact on the decision to treat with radiotherapy (e.g. previous inflammatory bowel disease, previous colo-rectal surgery, significant bladder instability or urinary incontinence) Bilateral hip prosthesis or fixation which would interfere with standard radiation beam configuration Patients who have undergone minor pelvic surgery will be eligible (eg appendicectomy, trans urethral resection of prostate (TURP), exploratory laparoscopy, haemorrhoidectomy, inguinal/femoral hernia repair)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prof. David Dearnaley
Organizational Affiliation
Institute of Cancer Research/RMHNHSFT
Official's Role
Principal Investigator
Facility Information:
Facility Name
Queen Elizabeth
City
Birmingham
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
Country
United Kingdom
Facility Name
Velindre Hospital
City
Cardiff
Country
United Kingdom
Facility Name
Ipswich
City
Ipswich
Country
United Kingdom
Facility Name
Clatterbridge Centre for Oncology
City
Liverpool
Country
United Kingdom
Facility Name
Royal Marsden NHSFT
City
London
Country
United Kingdom
Facility Name
Freeman Hospital
City
Newcastle
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
26104940
Citation
Harris VA, Staffurth J, Naismith O, Esmail A, Gulliford S, Khoo V, Lewis R, Littler J, McNair H, Sadoyze A, Scrase C, Sohaib A, Syndikus I, Zarkar A, Hall E, Dearnaley D; PIVOTAL Trialists. Consensus Guidelines and Contouring Atlas for Pelvic Node Delineation in Prostate and Pelvic Node Intensity Modulated Radiation Therapy. Int J Radiat Oncol Biol Phys. 2015 Jul 15;92(4):874-83. doi: 10.1016/j.ijrobp.2015.03.021. Epub 2015 Mar 30.
Results Reference
background
PubMed Identifier
30528653
Citation
Dearnaley D, Griffin CL, Lewis R, Mayles P, Mayles H, Naismith OF, Harris V, Scrase CD, Staffurth J, Syndikus I, Zarkar A, Ford DR, Rimmer YL, Horan G, Khoo V, Frew J, Venkitaraman R, Hall E. Toxicity and Patient-Reported Outcomes of a Phase 2 Randomized Trial of Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer (PIVOTAL). Int J Radiat Oncol Biol Phys. 2019 Mar 1;103(3):605-617. doi: 10.1016/j.ijrobp.2018.10.003. Epub 2018 Dec 6.
Results Reference
result

Learn more about this trial

A Study of Prostate and pelvIs Versus prOsTate Alone Treatment for Locally Advanced Prostate Cancer

We'll reach out to this number within 24 hrs