Management of Castration-Resistant Prostate Cancer with Oligometastases

NCT02685397 | Active Not Recruiting Phase 2

• 1 other identifier: PCS IX
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 11

Brief 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. 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.

Conditions

Castration-resistant Prostate Cancer Patients with Oligometastases

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression-free Survival

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

  5 years

Secondary Outcomes (11)

• Quality of Life

  5 years

• Quality of Life - Fatigue

  5 years

• Quality of Life - Pain

  5 years

• Toxicity

  5 years

• Prostate Cancer Specific Survival

  5 years

Study Arms (2)

LHRH agonist + Enzalutamide

ACTIVE COMPARATOR

Subjects will receive LHRH agonist in combination with the new generation of hormonal therapy (enzalutamide, 40mg)

Drug: Leuprolide Acetate; Drug: Goserelin Acetate; Drug: Triptorelin; Drug: Enzalutamide

LHRH agonist + Enzalutamide + SBRT

EXPERIMENTAL

Subjects will receive LHRH agonist in combination with the new generation of hormone therapy (enzalutamide, 40mg) plus the additional SBRT treatment

Drug: Leuprolide Acetate; Drug: Goserelin Acetate; Drug: Triptorelin; Drug: Enzalutamide; Radiation: Stereotactic Body Radiation Therapy

Interventions

Leuprolide Acetate DRUG

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.

Also known as: Eligard, Lupron

LHRH agonist + Enzalutamide; LHRH agonist + Enzalutamide + SBRT

Goserelin Acetate DRUG

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.

Also known as: ZOLADEX

LHRH agonist + Enzalutamide; LHRH agonist + Enzalutamide + SBRT

Triptorelin DRUG

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.

Also known as: Trelstar

LHRH agonist + Enzalutamide; LHRH agonist + Enzalutamide + SBRT

Enzalutamide DRUG

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.

Also known as: Xtandi

LHRH agonist + Enzalutamide; LHRH agonist + Enzalutamide + SBRT

Stereotactic Body Radiation Therapy RADIATION

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.

Also known as: SBRT

LHRH agonist + Enzalutamide + SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;
• i. 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:

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Sir Mortimer B. Davis - Jewish General Hospital: lead

Study Sites (11)

BC CANCER Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Nova Scotia Cancer Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program - London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Hopital Charles-Lemoyne

Longueuil, Quebec, J4V2H1, Canada

Location

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

Montreal, Quebec, H2L 4M1, Canada

Location

Jewish General Hospital, McGill University

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

Location

CHU de Quebec-Universite Laval

Québec, Quebec, G1R 2J6, Canada

Location

Centre Hospitalier régional de Trois-Rivières

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Related Publications (1)

• 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.

  PMID: 40907514 DERIVED

MeSH Terms

Interventions

Leuprolide; luprolide acetate gel depot; Goserelin; Triptorelin Pamoate; enzalutamide; Radiosurgery

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Tamim Niazi, MD

  Jewish General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 3, 2016
• First Posted: February 18, 2016
• Study Start: October 1, 2016
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): August 1, 2041
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11)