Trial Summary
What is the purpose of this trial?This trial focuses on frequent health assessments and monitoring for older men with prostate cancer to identify and manage health issues early, aiming to improve patient outcomes.
Is the drug GA+M Intervention, GA+RSM intervention, RSM intervention (also known as Lynparza, AZD-2281, MK-7339, KU0059436) a promising treatment for prostate cancer?Yes, the drug Lynparza (also known as AZD-2281, MK-7339, KU0059436) is considered promising for prostate cancer, especially in cases that are resistant to other treatments. It is part of a group of drugs called PARP inhibitors, which have shown effectiveness in improving survival and slowing disease progression in prostate cancer patients.126913
What safety data is available for the supportive care intervention for prostate cancer?The safety data for the supportive care intervention, specifically the combination of olaparib (also known as Lynparza, AZD-2281, MK-7339, KU0059436) and radium-223, is derived from a Phase I study. In this study, dose-limiting toxicities included cytopenias, fatigue, and nausea. The recommended phase 2 dose (RP2D) of olaparib was established at 200 mg orally twice daily with radium-223. The most common treatment-related adverse events were fatigue (92%) and anemia (58%). The combination was deemed safe at the RP2D, with early clinical benefits observed, warranting further investigation in a phase II study.3451114
What data supports the idea that Supportive Care Intervention for Prostate Cancer is an effective treatment?The available research shows that combining the drug olaparib with another drug called abiraterone significantly helps patients with prostate cancer live longer without the disease getting worse. This combination was tested in a study and showed better results compared to using other treatments alone. This suggests that the Supportive Care Intervention, which includes olaparib, can be an effective option for treating prostate cancer.3781012
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should be starting or have recently started an ARAT, or be switching ARATs due to progression or toxicity.
Eligibility Criteria
This trial is for men aged 70 or older with metastatic prostate cancer who are starting ARAT treatment. They must be able to give written consent and have a working phone. It's not for those who can't speak English, have a life expectancy under 3 months, or major neuropsychiatric issues like severe depression or dementia.Treatment Details
The TOPCOP3 study tests the effectiveness of geriatric assessment and management (GA+M), remote symptom monitoring (RSM), both interventions together (GA+RSM), or neither. This pilot RCT aims to gather data on these supportive care methods to plan larger trials.
4Treatment groups
Active Control
Group I: RSM InterventionActive Control1 Intervention
RSM Intervention All participants in the RSM intervention arm will receive once-weekly symptom monitoring via email-based surveys using the 9-item Edmonton Symptom Assessment Scale within a secure customized REDCap interface. If patients prefer, weekly telephone calls will be done instead by a research assistant to elicit If there are moderate or severe symptoms (score of 4+ out of 10), an oncology nurse will obtain more detailed symptom information and provide evidence-based symptom-targeted recommendations using the pan-Canadian Oncology Symptom Triage and Remote Support (COSTaRS) Practice Guide. Symptom monitoring will continue for 6 months or discontinuation of treatment.
Group II: GA+M InterventionActive Control1 Intervention
GA+M intervention arm All participants in the GA+M intervention arm will undergo a standardized GA by a trained nurse and geriatrician. The GA will include 8 domains (comorbidity, medication review, function, falls risk, nutrition, social supports, cognition, and mood) similar to our 5C protocol.
Based on any detected abnormalities or issues, a standardized set of strategies will be implemented (e.g. increased falls risk will lead to detailed assessment of balance and gait, consideration of gait aid, and referral to outpatient physiotherapy). This follows the standard approach to implementing GA similar to recent trials in geriatric oncology including 5C. Telephone follow-ups at 1, 3 and 6 months by the nurse and review with the geriatrician as needed will be done to ensure identified issues have been addressed.
Group III: GA+RSM interventionActive Control1 Intervention
GA+RSM Combination Participants will receive both strategies as detailed above, with a GA at baseline.
Group IV: ControlActive Control1 Intervention
Control Usual care consists of brief verbal education and a drug pamphlet to all patients when starting an ARAT. There is no GA+M and no RSM at either site. Patients have access to a 24x7 oncology nursing line or a 24/7 pharmacy line.
GA+M Intervention is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Lynparza for:
- Ovarian cancer
- Breast cancer
- Fallopian tube cancer
- Peritoneal cancer
- Pancreatic cancer
- Prostate cancer
🇺🇸 Approved in United States as Lynparza for:
- Ovarian cancer
- Breast cancer
- Fallopian tube cancer
- Peritoneal cancer
- Pancreatic cancer
- Prostate cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
University Health Network - Princess Margaret Cancer CentreToronto, Canada
Sunnybrook Health Sciences CentreToronto, Canada
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Who is running the clinical trial?
University Health Network, TorontoLead Sponsor
References
Phase II trial assessing granulocyte-macrophage-colony stimulating factor, ketoconazole plus mitoxantrone in metastatic castration-resistant prostate cancer progressing after docetaxel treatments. [2018]This study evaluated objective response and safety for the combination of granulocyte macrophage-colony stimulating factor (GM-CSF), ketoconazole, and mitoxantrone in castration-resistant prostate cancer (CRPC) patients who previously failed docetaxel-based chemotherapy.
Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. [2021]Enzalutamide (MDV3100) is a second-generation androgen receptor antagonist that improves survival in metastatic, castration-resistant prostate cancer (mCRPC). Alternatives include chemotherapy, radiation, immunotherapy and abiraterone.
Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: An Open-label Phase 1 Study. [2018]ODM-201 is a novel second-generation androgen receptor inhibitor for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
Therapy Update for Metastatic Castration-Resistant Prostate Cancer. [2017]To provide an overview of the efficacy, tolerability, drug interactions, dosing, and administration issues associated with enzalutamide, abiraterone, and radium-223 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial. [2022]In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment.
Phase 2 Study of Weekly Paclitaxel Plus Estramustine in Metastatic Hormone-Refractory Prostate Carcinoma: ECOG-ACRIN Cancer Research Group (E1898) Trial. [2019]This multicenter phase 2 study assessed the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer (CRPC).
Abiraterone-Olaparib Combo Aids Men with mCRPC. [2019]Recent findings from a phase II trial suggest that combining the antiandrogen abiraterone and the PARP inhibitor olaparib significantly improves progression-free survival among patients with metastatic castration-resistant prostate cancer, regardless of their homologous recombination repair-mutation status.
Prognostic Association of Prostate-specific Antigen Decline with Clinical Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide in a Randomized Clinical Trial. [2021]In the PREVAIL study, enzalutamide provided significant improvements versus placebo in clinical outcomes in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC). The association of post-treatment prostate-specific antigen (PSA) decline with clinical outcomes may provide important prognostic information.
Intensification of Systemic Therapy in Addition to Definitive Local Treatment in Nonmetastatic Unfavourable Prostate Cancer: A Systematic Review and Meta-analysis. [2022]Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or unfavourable nonmetastatic prostate cancer (nmPC).
A real-world retrospective analysis of the management of metastatic castrate-resistant prostate cancer in Ontario, Canada from 2010 - 2018. [2023]We sought to quantify mCRPC patient treatment patterns and survival across multiple lines of therapy after prior androgen-receptor-axis-targeted therapy (ARAT) failure.
A Phase I Study of Combination Olaparib and Radium-223 in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) with Bone Metastases (COMRADE). [2023]Given that radium-223 is a radiopharmaceutical that induces DNA damage, and olaparib is a PARP inhibitor that interferes with DNA repair mechanisms, we hypothesized their synergy in metastatic castration-resistant prostate cancer (mCRPC). We sought to demonstrate the safety and efficacy of olaparib + radium-223. We conducted a multicenter phase I 3+3 dose escalation study of olaparib with fixed dose radium-223 in patients with mCRPC with bone metastases. The primary objective was to establish the RP2D of olaparib, with secondary objectives of safety, PSA response, alkaline phosphatase response, radiographic progression-free survival (rPFS), overall survival, and efficacy by homologous recombination repair (HRR) gene status. Twelve patients were enrolled; all patients received a prior androgen receptor signaling inhibitor (ARSI; 100%) and 3 patients (25%) prior docetaxel. Dose-limiting toxicities (DLT) included cytopenias, fatigue, and nausea. No DLTs were seen in the observation period however delayed toxicities guided the RP2D. The RP2D of olaparib was 200 mg orally twice daily with radium-223. The most common treatment-related adverse events were fatigue (92%) and anemia (58%). The rPFS at 6 months was 58% (95% confidence interval, 27%-80%). Nine patients were evaluable for HRR gene status; 1 had a BRCA2 alteration (rPFS 11.8 months) and 1 had a CDK12 alteration (rPFS 3.1 months). Olaparib can be safely combined with radium-223 at the RP2D 200 mg orally twice daily with fixed dose radium-223. Early clinical benefit was observed and will be investigated in a phase II study.
Survival outcomes and prognostic factors for first-line abiraterone acetate or enzalutamide in patients with metastatic castration-resistant prostate cancer. [2023]To investigate the survival outcomes of metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line novel androgen receptor axis-targeted therapies (ARATs) and prognostic factors for patient survival.
Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis. [2023]To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT.
Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial. [2023]In patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial, darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable safety/tolerability profile. This post hoc analysis of ARAMIS evaluated efficacy and safety in patients by number of comorbidities and concomitant medications.