5500/20 vs. SABR or Brachytherapy for PRimary OligoMetastatic Prostate Cancer Treatment (PROMPT)

British Columbia Cancer Agency168 enrolled

Overview

We will investigate whether ultrahypofractionation using stereotactic ablative radiotherapy (SABR) or brachytherapy is as well-tolerated as moderately hypofractionated external beam radiotherapy (EBRT) for treating the prostate in patients with oligometastatic prostate cancer. Secondary aims include assessment of progression-free survival (PFS) and overall survival (OS) as well as cost-effectiveness. We hypothesize that ultrahypofractionation will maintain favorable toxicity profiles and quality of life while achieving comparable or better efficacy, thereby providing a convenient and cost-effective alternative to moderately hypofractionated EBRT.

Men newly diagnosed with low volume oligometastatic prostate cancer defined as fewer than 5 bone metastases and/or non regional lymph node involvement who agree to treatment of the primary cancer with radiation will be randomized between standard moderately hypofractionated external radiotherapy (5500 centiGray/20 fractions as per Stampede trial) and one of 3 alternatives: stereotactic body radiotherapy (SABR) to deliver 36 Gy/5 fractions, or low dose rate Iodine 125 permanent seed implant or a single high dose rate temporary implant. The trial will take place in 4 regional cancer centers of British Columbia Cancer Agency, with each center choosing their preferred alternative to 5500/20. To achieve 4 equally sized treatment arms, each randomization is weighted 3:1 for 42 patients in each arm and 168 total accrual. The primary endpoint is urinary quality of life as assessed by the International Prostate Symptom Score (IPSS) . As the typical acute symptoms from each of these radiation modalities has a unique time course, assessments are done at 6 different points during the first 2 years. Secondary endpoints are global quality of life as assessed by Expanded Prostate Cancer Index (EPIC) urinary, bowel and sexual scores, progression free survival, overall survival and cost effectiveness.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Interventions

Hypofractionated external beam radiotherapyRADIATION

5500 cGy/20 fractions delivered 5 days per week over 4 weeks

High dose rate brachytherapyRADIATION

A single fraction of 19 Gy is delivered from an automated afterloading Iridium-192 source via interstitial catheters placed under ultrasound guidance

Permanent seed implantRADIATION

Iodine-125 radioactive seeds are implanted permanently in the prostate in a single procedure under transrectal ultrasound guidance

Stereotactic body radiotherapyRADIATION

External radiation using SABR technology delivers 36.25 Gy to the prostate in 5 fractions given either once weekly for 5 weeks or every second day over 2 weeks.

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Able to provide informed consent * European Cooperative Oncology Group performance status 0 to 2 * Medically fit for all protocol treatment and follow-up * Histologically confirmed adenocarcinoma of the prostate * Newly diagnosed any Tumor stage, any Nodal stage but with oligo metastases * No prior therapy for prostate cancer apart from androgen deprivation * Able to complete the necessary investigations prior to randomization (History and physical examination, PSA) * Able to complete the necessary investigations prior to start of Radiotherapy (Transrectal ultrasound-guided biopsy or equivalent, CT chest, abdomen \& pelvis or MRI abdomen and pelvis, and Bone scan) * Planned for long-term androgen deprivation therapy (greater than 9 months in duration) * Patient is able and willing to complete the quality of life questionnaires, and other assessments that are a part of this study Exclusion Criteria: * High metastatic burden defined as 5 or more bone metastases or visceral metastases * Abnormal liver function * Contraindications to EBRT such as active inflammatory bowel disease or previous pelvic radiation Contraindications to brachytherapy including: * Medically unfit for anesthesia, * International Prostate Symptom Score (IPSS) greater than 20 * Poor urinary flow with peak flow rate less than10 mL per second or post-void residual greater than 25 per cent of voided volume (when uroflowmetry available) * Prostate volume greater than 60cc after maximal cytoreduction * Pubic arch interference * Transurethral resection of prostate (TURP) within 12 weeks of brachytherapy

Locations (4)

British Columbia Cancer Agency Center for the Southern Interior

Kelowna, British Columbia, Canada

RECRUITING

Fraser Valley Cancer Center

Surrey, British Columbia, Canada

NOT_YET_RECRUITING

Vancouver Cancer Center

Vancouver, British Columbia, Canada

RECRUITING

Vancouver Island Cancer Center

Victoria, British Columbia, Canada

RECRUITING

Outcomes

Primary Outcomes

Urinary symptoms

International Prostate Symptom score (0/35), higher worse

Time frame: Baseline to 2 years

Secondary Outcomes

Expanded Prostate Cancer Index (EPIC) urinary domain

Urinary Quality of life, 0/100 higher score better

Time frame: Baseline to 2 years

EPIC bowel domain

Bowel quality of life, 0/100, higher score better. Series of validated questions concerning urgency, frequency, consistency, leakage, presence of blood and pain with bowel movements and then rates how big a problem each symptom was (0-5)

Time frame: Baseline to 2 years

EPIC sexual domain

Sexual quality of life, 0/100, higher score better. Series of validated questions concerning frequency and quality of erections, presence of morning erections, ability to engage in sexual activity or intercourse, rates ability and then rates importance of each issue to the patient.

Time frame: Baseline to 2 years

Biochemical failure (time to increase in prostate specific antigen (ng/ml) to 50% > nadir

Progression free survival measured as time to Prostate Specific Antigen (PSA) rise by 50% \> nadir

Time frame: Baseline to 3 years

Distant metastatic failure

Progression free survival measured as time to new or progressive bone metastases

Time frame: Baseline to 3 years

Nodal progression

Progression free survival measured as new or progressive adenopathy on imaging

Time frame: Baseline to 3 years

Overall survival

Overall survival regardless of cause of death

Time frame: 3 years

Cause specific survival

Death from prostate cancer

Time frame: Within 3 years of treatment

Cost effectiveness

Analysis of primary treatment costs and secondary treatment costs at time of progression

Time frame: 3 years

5500/20 vs. SABR or Brachytherapy for PRimary OligoMetastatic Prostate Cancer Treatment (PROMPT)

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts