Management of Oligoprogressive Castration Resistant Prostate Cancer (PCS X)

NCT04070209 | Recruiting Phase 2

• 1 other identifier: PCS X
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 10

Brief Summary

This is the first pilot phase II trial assessing the response of SBRT layered on Darolutamide (BAY1841788) on RPFS and deferring palliative second line systemic therapy in M0CRPC with oligoprogression.

Conditions

Metastatic Prostate Cancer; Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression-free Survival

  Time from first day of SBRT until confirmed second radiological progression or start of new antineoplastic therapy

  5 years

Secondary Outcomes (10)

• Functional Assessment of Cancer Therapy-Prostate

  5 years

• Quality of Life - Fatigue

  5 years

• Quality of Life - Pain

  5 years

• Toxicity of ODM-201

  5 years

• Time to Subsequent Systemic Antineoplastic Therapy

  5 years

Study Arms (1)

Darolutamide (BAY1841788)+ SBRT

EXPERIMENTAL

CRPC subjects will receive LHRH agonist in combination with the new generation of hormonal therapy Darolutamide (300mg). Subjects who progress on LHRH + Darolutamide and develop oligometastases will receive SBRT

Drug: Darolutamide (BAY1841788); Radiation: SBRT

Interventions

Darolutamide (BAY1841788) DRUG

Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg.

Also known as: ODM-201

Darolutamide (BAY1841788)+ SBRT

SBRT RADIATION

SBRT will consist of 2-5 fractions of highly targeted radiation therapy delivered every other day. The radiation component will be completed in 4-10 days.

Darolutamide (BAY1841788)+ SBRT

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
• M0CRPC at study entry defined as follows:
• Ongoing androgen deprivation therapy with a LHRH agonist or bilateral orchiectomy (i.e., surgical or medical castration);
• Serum testosterone level ≤ 1.7 nmol/L (50 ng/dL) at the Screening visit;
• PSA progression defined by a minimum of two subsequent 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)
• PSA doubling time of 10 months or less,
• M0 assessed by conventional imaging (CT/MRI + bone scan).
• Prior cytotoxic chemotherapy for prostate cancer in adjuvant setting post radical therapy is allowed;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or Karnofsky performance status of \> 80% or higher;
• Estimated life expectancy of ≥ 6 months;
• Ability to swallow the study drug whole and comply with study.
• Patients should not have been previously exposed to other ARATs (Abiraterone, Enzalutamide, Apalutamide)
• ≤ 5 metastatic sites (on conventional imaging);
• ≤ 4 tumors within any given organ system, excluding brain (e.g. up to 4 bone metastases, or 4 lung metastases);
• All sites of disease must be amenable to SBRT with no history of the metastases being irradiated (radiation exposure prior to the development of the metastases is permitted as long as the radiation exposure was not intended for the metastases. For example, if there is prior pelvic radiation to the prostate and a subsequent iliac metastasis develops within the previously irradiated pelvic radiation field, then the iliac metastasis would be eligible per the institution policy and practice);

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;
• 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);
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal and total bilirubin \> 1.5 times the upper limit of normal at the Screening visit;
• Creatinine \> 2 times the upper limit of normal at the Screening visit;
• Clinically significant cardiovascular disease including:
• Stroke or myocardial infarction within 6 months;
• Uncontrolled angina within 6 months;
• Coronary/peripheral artery bypass graft within 6 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 Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
• Uncontrolled hypertension as indicated by a resting systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg at screening. Patients may be re-screened after adjustments of antihypertensive medications;
• Bradycardia as indicated by a heart rate of \< 50 beats per minute on the Screening ECG;
• Gastrointestinal disorder or procedure which expects to interfere significantly with absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months);
• Major surgery within 4 weeks of enrollment (Day 1 Visit);

Sponsors & Collaborators

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

Study Sites (10)

Prostate Cancer Centre

Calgary, Alberta, T2V 1P9, Canada

RECRUITING

Centre of Applied Urology Research

Halifax, Nova Scotia, B3H 2Y9, Canada

RECRUITING

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

RECRUITING

Service d'urologie et Centre de la prostate

Longueuil, Quebec, J4V 2H3, Canada

RECRUITING

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

RECRUITING

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

Sir Mortimer JGH

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

L'Hôtel-Dieu de Québec (CHUQ)

Québec, Quebec, G1R 2J6, Canada

RECRUITING

Hôpital Fleurimont (CHUS)

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

Centre hospitalier affilié universitaire régional (CHAUR)

Trois-Rivières, Quebec, G8Z 3R9, Canada

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Tamim Niazi, MD

  Jewish General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paola Diego

CONTACT

514-340-8222; paola.diego.ccomtl@ssss.gouv.qc.ca

Study Design

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

Study Record Dates

• First Submitted: August 24, 2019
• First Posted: August 28, 2019
• Study Start: October 19, 2020
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: December 4, 2024

Record last verified: 2024-12

Locations

CA (10)