AzTrials
AzTrials

Castration-resistant Prostate Cancer Patients with OligometastasesPhase 2/3PCS IXNCT02685397

Management of Castration-Resistant Prostate Cancer with Oligometastases

A Phase 2/3 study testing Leuprolide Acetate, Goserelin Acetate and Triptorelin in people with Castration-resistant Prostate Cancer Patients with Oligometastases, run by Sir Mortimer B. Davis - Jewish General Hospital at 11 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This adaptive phase II/III randomized trial is designed to demonstrate that eradication of oligometastases by SBRT is a promising and emerging way to delay disease progression and postpone second line systemic therapies in castration-resistant prostate cancer (CRPC) patients. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Leuprolide Acetate, Goserelin Acetate and Triptorelin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
11 sitesCanada
Study dates
Oct 2016to Aug 2041
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 or older and willing and able to provide informed consent;
  • Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
  • Ongoing androgen deprivation therapy with a Gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy (i.e., surgical or medical castration);
  • Patients who have not had a bilateral orchiectomy must have a plan to maintain effective GnRH analogue therapy for the duration of the trial;
  • Serum testosterone level ≤ 1.7 nmol/L (50 ng/dL) at the Screening visit;
  • Patients receiving bisphosphonate therapy/Xgeva must have been on stable doses for at least 4 weeks;
Show all 24Show fewer
  • Progressive disease at study entry defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy as defined in eligibility criterion #3:
  • PSA progression defined by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination. Patients who received an anti-androgen must have progression after withdrawal (≥ 4 weeks since last flutamide or ≥ 6 weeks since last bicalutamide or nilutamide). The PSA value at the Screening visit should be ≥ 2 μg/L (2 ng/mL);
  • Metastatic disease documented by bone lesions on bone scan or by measurable soft tissue disease by CT/MRI. Patients whose disease spread is limited to regional pelvic lymph nodes, and previously radiated, are not eligible;
  • Up to 5 metastatic sites ii. ≤ 4 tumours within any given organ system, excluding brain and liver (e.g. up to 4 bone metastases, or 4 lung metastases) iii. All sites of disease must be amenable to SBRT with no history of the metastases being irradiated; iv. In the case of a suspicious lesion in an unusual location such as lung or thoracic lymph nodes (without other abdominal lymph nodes), a biopsy should confirm prostate cancer origin.
  • No prior cytotoxic chemotherapy for prostate cancer;
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or Karnofsky performance status of > 70% or higher;
  • Patients and their female partners of childbearing potential must be willing to use two forms of contraception (one of which must include a condom as a barrier method of contraception during sexual activity) throughout the duration of the study starting at screening and continuing for 3 months after the last dose of study drug or per local guidelines where these require additional description of birth control methods. These contraceptive methods must include the following:
  • The use of condoms (barrier method)
  • AND one of the following:
  • the use of oral, injected or implanted hormonal methods of contraception by a female partner;
  • placement of an intrauterine device (IUD) or intrauterine system (IUS) by a female partner;
  • additional barrier method, such as occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository by a female partner;
  • tube ligation in the female partner;
  • vasectomy or other procedure resulting in infertility (eg. bilateral orchiectomy) for ≥ 6 months.
  • If the patient's partner is a pregnant woman, the patient must use a condom during sexual activity during and for 3 months after treatment with enzalutamide.
  • Patients must agree to not donate sperm while taking study drug
  • Estimated life expectancy of ≥ 6 months;
  • Ability to swallow the study drug whole and comply with study.

Who cannot join

  • Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment;
  • Known or suspected brain metastasis or active leptomeningeal disease;
  • History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer;
  • Absolute neutrophil count < 1,500/μL, platelet count < 100,000/μL, or hemoglobin < 5.6 mmol/L (9 g/dL) at the Screening visit (NOTE: patients may not have received any growth factors within 7 days or blood transfusions within 28 days of the hematologic laboratory values obtained at the Screening visit);
  • Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal at the Screening visit;
  • Creatinine > 177 μmol/L (2 mg/dL) at the Screening visit;
Show all 35Show fewer
  • Albumin < 30 g/L (3.0 g/dL) at the Screening visit;
  • History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma). Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (Day 1 visit);
  • Clinically significant cardiovascular disease including:
  • Myocardial infarction within 6 months;
  • Uncontrolled angina within 3 months;
  • Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within three months results in a left ventricular ejection fraction that is ≥ 45%;
  • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
  • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
  • Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mmHg) at the Screening visit;
  • Bradycardia as indicated by a heart rate of < 50 beats per minute on the Screening ECG;
  • Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the Screening visit.
  • Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months);
  • Major surgery within 4 weeks of enrollment (Day 1 Visit);
  • Use of opiate analgesics (eg. morphine, fentanyl, etc.) for pain from prostate cancer within 4 weeks of enrollment (Day 1 visit). This does not apply to non-morphine drugs like codeine;
  • Radiation therapy for treatment of the primary tumour within 3 weeks of enrollment (Day 1 visit);
  • Radiation or radionuclide therapy for treatment of metastasis;
  • Primary disease not treated
  • More than 5 metastases
  • Hormone naïve prostate cancer patients
  • Treatment with flutamide within 4 weeks of enrollment (Day 1 visit);
  • Treatment with bicalutamide or nilutamide within 6 weeks of enrollment (Day 1 visit);
  • Treatment with 5-α reductase inhibitors (finasteride, dutasteride), estrogens, cytproterone within 4 weeks of enrollment (Day 1 visit)
  • Treatment with systemic biologic therapy for prostate cancer (other than approved bone targeted agents and GnRH-analogue therapy) or other agents with anti-tumour activity within 4 weeks of enrollment (Day 1 visit);
  • History of prostate cancer progression on ketoconazole;
  • Prior use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., BMS 641988);
  • Participation in a previous clinical trial of enzalutamide;
  • Use of an investigational agent within 4 weeks of enrollment (Day 1 visit);
  • Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within four weeks of enrollment (Day 1 visit);
  • Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Canada11 sites

  • Nova Scotia Cancer Centre

    Halifax, Nova Scotia, B3H 1V7

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • London Regional Cancer Program - London Health Sciences Centre

    London, Ontario, N6A 5W9

  • Hopital Charles-Lemoyne

    Longueuil, Quebec, J4V2H1

  • Centre Hospitalier de l'Université de Montréal (CHUM) - Hopital Notre Dame

    Montreal, Quebec, H2L 4M1

  • Jewish General Hospital, McGill University

    Montreal, Quebec, H3T 1E2

  • McGill University Health Center

    Montreal, Quebec, H4A 3J1

  • CHU de Quebec-Universite Laval

    Québec, Quebec, G1R 2J6

  • Centre Hospitalier régional de Trois-Rivières

    Trois-Rivières, Quebec, G8Z 3R9

  • BC CANCER Vancouver

    Vancouver, British Columbia, V5Z 4E6

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: The Role of Stereotactic Body Radiotherapy in the Management of Castration-Resistant Prostate Cancer with Oligometastases: an Adaptive Phase II/III Randomized Trial.

This adaptive phase II/III randomized trial is designed to demonstrate that eradication of oligometastases by SBRT is a promising and emerging way to delay disease progression and postpone second line systemic therapies in castration-resistant prostate cancer (CRPC) patients. Only CRPC patients with an oligometastatic recurrence will be eligible to take part in this trial. All participating patients will receive either the standard of care (i.e. LHRH agonist in combination with the new generation of hormonal therapy [Enzalutamide]) or the experimental treatment (i.e. LHRH agonist in combination with the new generation of HT [Enzalutamide] plus the additional SBRT treatment). The patients will undergo different evaluations before treatment, such as imaging to confirm oligometastatic recurrence and blood tests. Patients will be stratified according to the location of metastasis (visceral [with or without bone metastases] vs. bone metastases alone) and PSA doubling time (≤ 3 vs. > 3 months). As per the standard of care, patients will have PSA testing performed every 6-12 weeks and re-imaging at 6, 9, 12, 18 and 24 months or at PSA progression, whichever occurs first.

Read the detailed description

Prostate cancer (PCa) is the most common type of cancer to affect men and, unfortunately, for the majority of PCa patients, death is attributed to metastatic disease. Lifelong androgen deprivation therapy (ADT) with LHRH agonists can help delay cancer progression in metastatic PCa patients. However, patients eventually become castration-resistant (disease progression despite ADT) and develop progressive metastatic disease. This in turn impacts the patient's quality of life and survival. Recently, a new generation of hormonal therapy (such as Enzalutamide) has become available to these castration-resistant prostate cancer (CRPC) patients. We believe that the benefits from this new generation of hormonal therapy can be prolonged in CRPC patients who develop oligometastases by treating the metastatic lesions using stereotactic body radiotherapy (SBRT). This new radiation technique allows for the treatment of many different metastases throughout the body in a very precise manner. This metastases-directed therapy is a new treatment option for patients with a limited number of metastases (less than 5) at the time of recurrence.

This adaptive phase II/III randomized trial is designed to demonstrate that eradication of oligometastases by the new technique SBRT is a promising and emerging way to delay disease progression and to postpone second line systemic therapies. Only patients with an oligometastatic recurrence after local treatment with curative intent will be eligible to take part in this trial. All participating CRPC patients with oligometastases will receive either the standard of care (i.e. LHRH agonist in combination with the new generation of hormonal therapy [Enzalutamide]) or the experimental treatment (i.e. LHRH agonist in combination with the new generation of HT [Enzalutamide] plus the additional SBRT treatment). The patients will undergo different evaluations before treatment, such as imaging to confirm oligometastatic recurrence and blood tests. Patients will be stratified according to the location of metastasis (visceral [with or without bone metastases] vs. bone metastases alone) and PSA doubling time (≤ 3 vs. > 3 months). As per the standard of care, patients will have PSA testing performed every 6-12 weeks and re-imaging at 6, 9, 12, 18 and 24 months or at PSA progression, whichever occurs first.

The primary objective of this study will be to evaluate the radiographic progression-free survival. We also want to determine the time to the start of second line systemic therapy, the prostate-cancer specific survival, the overall survival as well as to assess the quality of life, the toxicity and the PSA response. This study is the first randomized study in this setting and will employ a randomized phase II design to determine if a larger scale phase III trial is needed, thus the phase II/III design. The Phase II will consist of 130 CRPC patients with oligometastases, and the phase III will consist of the already randomized 130 patients plus an estimated 244 patients for a total sample size of 374 patients. This study will be conducted through the Genitourinary Radiation Oncology Group of Quebec (GROUQ) in different radiation oncology centres across Canada and the recruitment should be completed within 30 months of activation.

Being tested
Leuprolide Acetate, Goserelin Acetate, Triptorelin, Enzalutamide, Stereotactic Body Radiation Therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Leuprolide AcetateDrug

    Also called Eligard, Lupron

    Luteinizing hormone releasing hormone (LHRH) agonist administered by subcutaneous injection. Only one of the LHRH agonists described here will be administered during the course of treatment.

  • Goserelin AcetateDrug

    Also called ZOLADEX

    Luteinizing hormone releasing hormone (LHRH) agonist administered by subcutaneous injection. Only one of the LHRH agonists described here will be administered during the course of treatment.

  • TriptorelinDrug

    Also called Trelstar

    Luteinizing hormone releasing hormone (LHRH) agonist administered by subcutaneous injection. Only one of the LHRH agonists described here will be administered during the course of treatment.

  • EnzalutamideDrug

    Also called Xtandi

    Anti-androgen medication for the treatment of metastatic castration-resistant prostate cancer. 160 mg (four 40 mg capsules) taken as a single oral daily dose, with or without food, until disease progression.

  • Stereotactic Body Radiation TherapyRadiation

    Also called SBRT

    Stereotactic body radiation therapy (SBRT) is a treatment modality in radiation oncology that delivers a very high dose of radiation to the tumour target with high precision using a single or a small number of fractions.

Study groups in NCT02685397
Study groupRoleWhat they receive
LHRH agonist + EnzalutamideActive comparatorSubjects will receive LHRH agonist in combination with the new generation of hormonal therapy (enzalutamide, 40mg)
Receives: Drug: Leuprolide Acetate; Drug: Goserelin Acetate; Drug: Triptorelin; Drug: Enzalutamide
LHRH agonist + Enzalutamide + SBRTExperimentalSubjects will receive LHRH agonist in combination with the new generation of hormone therapy (enzalutamide, 40mg) plus the additional SBRT treatment
Receives: Drug: Leuprolide Acetate; Drug: Goserelin Acetate; Drug: Triptorelin; Drug: Enzalutamide; Radiation: Stereotactic Body Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Radiographic Progression-free Survival

    Time from randomization until disease progression confirmed by radiographic imaging or the start of new antineoplastic therapy.

    Measured: 5 years

Secondary outcomes (11)

  1. Quality of Life

    Evaluate the impact of the treatment on the patient's quality of life using the FACT-P questionnaire

    Measured: 5 years

  2. Quality of Life - Fatigue

    Evaluate the impact of the treatment on the patient's quality of life using the Brief Fatigue Inventory (BFI) questionnaire

    Measured: 5 years

  3. Quality of Life - Pain

    Evaluate the impact of the treatment on the patient's quality of life using the Brief Pain Inventory (BPI) questionnaire

    Measured: 5 years

  4. Toxicity

    To determine acute and late toxicity due to radiotherapy, scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.3

    Measured: 5 years

  5. Prostate Cancer Specific Survival

    Time from randomization until death due to prostate cancer.

    Measured: 5 years

  6. Time to Skeletal-related Event

    Time from randomization until the occurrence of a skeletal related event (SRE).

    Measured: 5 years

  7. Overall Survival

    Time from randomization until death from any cause.

    Measured: 5 years

  8. Local Control

    To evaluate the impact of SBRT on oligometastases progression by radiographic imaging or the start of new antineoplastic therapy.

    Measured: 5 years

  9. Time to Systemic Antineoplastic Therapy

    Time from randomization to the administration of subsequent antineoplastic systemic therapy

    Measured: 5 years

  10. PSA response

    To evaluate PSA or the onset of biochemical failure

    Measured: 5 years

  11. Predictive Value of Biomarkers

    To evaluate the predictive value of the biomarkers in radiographic progression-free survival by analyzing for the presence or absence of biomarkers and evaluating for possible correlation with radiographic progression-free survival.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2016 (estimated)
  2. Study startOct 2016
  3. Primary completionApr 2027 (estimated)
  4. Study completionAug 2041 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02685397
Sponsor's protocol ID
PCS IX
Acronym
PCS IX
Status last verified
Dec 2024
First submitted
3 Feb 2016
Last updated
4 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
Individual data sharing
No

Publications

  • Niazi T, Saad F, Tisseverasinghe S, Koul R, Thibault I, Chung PWM, Wakil G, Lock M, Delouya G, Bahoric B, Feifer A, Agnihotram VR, Tsakiridis T, Cury FL, Dahmane R, Patil NG, Tyldesley S. Metastases-directed therapy in addition to standard systemic therapy in oligometastatic castration-resistant prostate cancer in Canada (GROUQ-PCS 9): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2025 Sep;26(9):1158-1167. doi: 10.1016/S1470-2045(25)00351-1.

    PubMed 40907514

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Leuprolide Acetate, Goserelin Acetate and Triptorelin in people with Castration-resistant Prostate Cancer Patients with Oligometastases, run by Sir Mortimer B. Davis - Jewish General Hospital at 11 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Radiographic Progression-free Survival (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02685397, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in