NCT01685190

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
124

participants targeted

Target at P75+ for phase_2 prostate-cancer

Timeline
Completed

Started Jun 2011

Longer than P75 for phase_2 prostate-cancer

Geographic Reach
1 country

7 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2011

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

October 26, 2011

Completed
11 months until next milestone

First Posted

Study publicly available on registry

September 14, 2012

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2013

Completed
6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
Last Updated

January 4, 2019

Status Verified

January 1, 2019

Enrollment Period

2.5 years

First QC Date

October 26, 2011

Last Update Submit

January 2, 2019

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

  • 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.

    18 weeks post treatment

Secondary Outcomes (7)

  • Ability to deliver 60Gy in 37 fractions to the pelvis using the varying radiotherapy planning techniques and delivery systems at the participating centres.

    2 yr

  • Late (1 and 2 year) toxicity

    2 yr

  • Patient Reported Outcomes

    2 yr

  • Biochemical progression free survival

    10 yr

  • Time to local progression

    10 yr

  • +2 more secondary outcomes

Study Arms (2)

Prostate Alone IMRT

ACTIVE COMPARATOR

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

Radiation: Prostate alone IMRT

Prostate & Pelvis IMRT

EXPERIMENTAL

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.

Radiation: Prostate and pelvis IMRT

Interventions

Prostate alone IMRTRADIATION

Participants will receive standard prostate IMRT of 74Gy in 37 fractions delivered over 7.5 weeks.

Prostate Alone IMRT
Prostate and pelvis IMRTRADIATION

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.

Prostate & Pelvis IMRT

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Queen Elizabeth

Birmingham, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Velindre Hospital

Cardiff, United Kingdom

Location

Ipswich

Ipswich, United Kingdom

Location

Clatterbridge Centre for Oncology

Liverpool, United Kingdom

Location

Royal Marsden NHSFT

London, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Related Publications (2)

  • 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.

    PMID: 26104940BACKGROUND

  • 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.

    PMID: 30528653RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Study Officials

  • Prof. David Dearnaley

    Institute of Cancer Research/RMHNHSFT

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 26, 2011

First Posted

September 14, 2012

Study Start

June 1, 2011

Primary Completion

December 1, 2013

Study Completion

December 1, 2019

Last Updated

January 4, 2019

Record last verified: 2019-01

Locations

GB(7)