Clinical trial NCT03784755: Local Ablative Therapy For Hormone Sensitive Oligometastatic Prostate Cancer
Official title: A Randomized Phase III Trial of Local Ablative Therapy For Hormone Sensitive Oligometastatic Prostate Cancer [PLATON]
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Prostate Cancer Metastatic
Keywords: Oligometastatic Hormone
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Canadian Cancer Society (CCS)
First posted: 2018-12-24
Enrollment: 409
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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 0-2
* 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 with palliative intent.
* 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

Primary outcomes:
measure: Failure-free Survival
timeFrame: 6 years
Secondary outcomes:
measure: Radiographic Progression-free Survival
timeFrame: 6 years
measure: Incidence of new metastases as first event
timeFrame: 6 years
measure: Overall Survival
timeFrame: 6 years
measure: Ablative treatment related adverse events (>/= grade 3) using CTCAE v5.0
timeFrame: 6 years
measure: Quality of Life measured by EORTC QLQ-C30
timeFrame: 6 years
measure: Quality of Life measured by Bone Metastases module (BM22)
timeFrame: 6 years
measure: Quality of Life measured by prostate (PR25) questionnaire module
timeFrame: 6 years
measure: Economic analysis measured by EQ-5D-5L
timeFrame: 6 years
measure: Economic analysis by determining an incremental cost-effectiveness ratio reported as a difference in cost per FFS-year between the 2 arms
timeFrame: 6 years
Other outcomes:
Locations:
city: Victoria
country: Canada
facility: BCCA - Victoria
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Partners - Credit Valley Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Sault Ste. Marie
country: Canada
facility: Algoma District Cancer Program
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l'Est-de-I'lle-de-Montreal
state: Quebec
city: Montreal
country: Canada
facility: CHUM-Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: The Jewish General Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Hotel-Dieu de Quebec
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, ON Canada
name: Patrick CF Cheung
role: STUDY_CHAIR
affiliation: The Jewish General Hospital, Montreal, QC Canada
name: M. Tamim Niazi
role: STUDY_CHAIR
References: