Local Ablative Therapy For Hormone Sensitive Oligometastatic Prostate Cancer (PLATON)

A Randomized Phase III Trial of Local Ablative Therapy For Hormone Sensitive Oligometastatic Prostate Cancer [PLATON]

The purpose of this study is to compare the effects of ablative therapy (radiation or surgery) to all sites of disease combined with standard treatments on prostate cancer, compared to the standard or usual treatments used to treat this disease.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer Metastatic
• Intervention / Treatment: Other: Standard of care; Radiation: Ablative Radiation Therapy

Detailed Description

The standard or usual treatment for this disease is systemic therapy, which includes androgen deprivation therapy (ADT) with or without chemotherapy or hormone therapy. Additionally, for some patients with specific disease features, standard treatment may also include ablative treatment (radiation or surgery) of the prostate gland if this was not completed prior to enrolling into this study.

Ablative Therapy is a procedure used to destroy cancer cells and tissue. In this study Stereotactic Body Radiation Therapy (SBRT) or surgery will be used to destroy prostate cancer metastases. It is not clear if ablative therapy (SBRT or surgery) to all sites of disease used in combination with standard systemic therapy can offer better results than standard treatment alone.

• Study Type: Interventional
• Enrollment (Estimated): 410
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wendy Parulekar; Phone Number: 613-533-6430; Email: wparulekar@ctg.queensu.ca

Study Locations

• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 6V5
      • Recruiting
      • BCCA - Vancouver Island Cancer Centre
      • Contact: Abraham S. Alexander; Phone Number: 77094 250 519-5575
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Recruiting
      • CancerCare Manitoba
      • Contact: Bashir Bashir; Phone Number: 204 578-2208
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Recruiting
      • QEII Health Sciences Centre
      • Contact: Nikhilesh Patil; Phone Number: 902 473-6185
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Recruiting
      • Royal Victoria Regional Health Centre
      • Contact: Adam Gladwish; Phone Number: 705 728-9090
    • Hamilton, Ontario, Canada, L8V 5C2
      • Recruiting
      • Juravinski Cancer Centre at Hamilton Health Sciences
      • Contact: Kimmen Quan
    • Mississauga, Ontario, Canada, L5M 2N1
      • Recruiting
      • Trillium Health Partners - Credit Valley Hospital
      • Contact: Andrew Chiang; Phone Number: 5115 905 813-1100
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Ottawa Hospital Research Institute
      • Contact: Scott Morgan; Phone Number: 70206 613 737-7700
    • Sault Ste. Marie, Ontario, Canada, P6B 0A8
      • Recruiting
      • Algoma District Cancer Program
      • Contact: Mohammad Rassouli; Phone Number: 4450 705 759-3434
    • Sudbury, Ontario, Canada, P3E 5J1
      • Recruiting
      • Health Sciences North
      • Contact: Ryan Carlson; Phone Number: 2451 705 522-6237
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • University Health Network
      • Contact: Peter Chung; Phone Number: 6522 416 946-4501
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Odette Cancer Centre
      • Contact: Patrick C.F. Cheung; Phone Number: 416 480-6165
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • The Jewish General Hospital
      • Contact: M. Tamim Niazi; Phone Number: 514 340-8288
    • Montreal, Quebec, Canada, H2X 3E4
      • Recruiting
      • CHUM-CEntre Hospitalier de l'Universite de Montreal
      • Contact: Maroie Barkati; Phone Number: 514 890-8254
    • Montreal, Quebec, Canada, H1T 2M4
      • Recruiting
      • CIUSSS de l'Est-de-I'lle-de-Montreal
      • Contact: Peter Vavassis; Phone Number: 514 252-3425
    • Quebec City, Quebec, Canada, G1R 2J6
      • Recruiting
      • Hotel-Dieu de Quebec
      • Contact: Isabelle Thibault; Phone Number: 418 691-5181
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Recruiting
      • Allan Blair Cancer Centre
      • Contact: Dilip Panjwani; Phone Number: 306 766-2296
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Recruiting
      • Saskatoon Cancer Centre
      • Contact: Ali El-Gayed; Phone Number: 306 655-2740

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologic diagnosis/confirmation of prostate adenocarcinoma and no evidence of small cell cancer.
• Stage IV at presentation or relapse after curative intent therapy, classification per AJCC 8th edition: M1 disease with ≤ 5 metastases
• ≤ 3 metastases in any non-bone organ system
• Zoladex must commence within 12 weeks prior to randomization or within 12 weeks after randomization.
• Radiology (CT/MRI chest/abdomen/pelvis) within 42 days of randomization
• Bone scan within 42 days of randomization
• All tumours (Primary prostate and metastases) must be amenable to local ablative therapy (radiation and/or surgery).
• Age ≥ 18
• ECOG performance 0-1
• Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life and economics questionnaires in either English or French
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
• Patients must be medically suitable for study treatments as assessed by the appropriate specialties: medical, radiation, and surgical
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up
• In accordance with CCTG policy, ablative therapy to metastases is to begin within 6 weeks after patient randomization
• Men of childbearing potential must have agreed to use a highly effective contraceptive method to prevent pregnancy while on study
• Patient must consent to provision of, and Investigator must confirm location of and commit to obtain a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative studies described in the protocol may be conducted. Where tissue exists but local centre regulations prohibit submission of blocks of tumour tissue, the approval of the CCTG must be sought prior to randomization of the first patient to allow cores (two 2 mm cores of tumour from the block) and slides (20 x 5 micron thick unstained slides) of representative tumour tissue to be substituted
• Patient must consent to provision of samples of whole blood (for cfDNA) in order that the specific correlative studies described in the protocol may be conducted.

Exclusion Criteria:

• Prior treatment with ADT in the neoadjuvant or adjuvant setting, unless treatment was discontinued ≥ 12 months prior to randomization AND total duration of treatment was ≤ 36 months (including expiry of last depot injection).
• Previously diagnosed recurrent/metastatic disease which has been already treated with any systemic therapy or radiotherapy
• Castration resistant prostate cancer, defined as rising PSA (per PCWG3) or radiographic progression in the setting of castrate levels of serum testosterone (< 1.7 nmol/L).
• Patients who present with de novo stage IV disease with pelvic lymphadenopathy as their only site of metastases (N1 M0), where the primary prostate has never been treated with curative intent prostate surgery or radiotherapy in the past.
• Inability to treat all sites of disease with local ablative therapy
• Patients with parenchymal brain metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1 (standard of care); Standard systemic therapy + Ablative therapy to untreated prostate primary for patients with low volume metastatic disease burden	Other: Standard of care; Patients continue to receive their current planned systemic therapy at the discretion of the treating physician
Experimental: Arm 2 (standard systemic therapy + ablative therapy)); Local Ablative therapy to all sites of disease (including untreated prostate primary) + Standard systemic therapy	Other: Standard of care; Patients continue to receive their current planned systemic therapy at the discretion of the treating physician; Radiation: Ablative Radiation Therapy; Undergo stereotactic radiotherapy and/or surgery to all sites of disease (oligometastases and primary prostate if previously untreated).; Other Names: SBRT; Stereotactic External Beam Irradiation; Stereotactic Radiotherapy; Stereotactic Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-free Survival	defined as the time from randomization to the time of the first occurrence.	6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Progression-free Survival	the comparison of these outcomes between the two treatment arms will be tested by the log-rank test	6 years
Incidence of new metastases as first event	the comparison of these outcomes between the two treatment arms will be tested by the log-rank test	6 years
Overall Survival	the comparison of these outcomes between the two treatment arms will be tested by the log-rank test	6 years
Ablative treatment related adverse events (>/= grade 3) using CTCAE v5.0		6 years
Quality of Life measured by EORTC QLQ-C30	It consists of both multi-item scales and single item measures, including five functioning domains, a global quality of life domain, three symptom domains and six single items. For each domain or single item measure a linear transformation will be applied to standardize the raw score to range between 0 and 100	6 years
Quality of Life measured by Bone Metastases module (BM22)	The BM22 has 22 questions consisting of the 4 subscales (painful sites (PS) and pain characteristics (PC) on the symptom scale and functional interference (FI) and psychosocial aspects (PA) on the functional scale). Modules, relevant subscales will also be linear transformed to standardize the raw score to range between 0 and 100 in accordance with the EORTC scoring manuals.	6 years
Quality of Life measured by prostate (PR25) questionnaire module	has 25 questions in four domains (urinary, bowel, sexual, and hormonal). Modules, relevant subscales will also be linear transformed to standardize the raw score to range between 0 and 100 in accordance with the EORTC scoring manuals.	6 years
Economic analysis measured by EQ-5D-5L	The robustness of the model results will be assessed using one-way and multi-way sensitivity analyses. Major drivers of medical care costs, namely hospitalization, chemotherapy and survival, will be varied ± 20%, to examine the impact on the base-case incremental cost effectiveness ratios (ICERs). Bootstrapping and the development of a cost-effectiveness acceptability curve will also be conducted.	6 years
Economic analysis by determining an incremental cost-effectiveness ratio reported as a difference in cost per FFS-year between the 2 arms		6 years

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: Canadian Cancer Society (CCS)
• Investigators: Study Chair: Patrick CF Cheung, Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, ON Canada; Study Chair: M. Tamim Niazi, The Jewish General Hospital, Montreal, QC Canada

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: December 19, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Oligometastatic Hormone
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PR20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No