Hormone + Radiation Therapy for Prostate Cancer
Palo Alto (17 mi)Overseen byPaul L Nguyen
Age: 18+
Sex: Male
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: NRG Oncology
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase III trial compares less intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in treating patients with high risk prostate cancer and low gene risk score. This trial also compares more intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in patients with high risk prostate cancer and high gene risk score. Apalutamide may help fight prostate cancer by blocking the use of androgen by the tumor cells. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving a shorter hormone therapy treatment may work the same at controlling prostate cancer compared to the usual 24 month hormone therapy treatment in patients with low gene risk score. Adding apalutamide to the usual treatment may increase the length of time without prostate cancer spreading as compared to the usual treatment in patients with high gene risk score.
Is the treatment combining hormone drugs and radiation therapy promising for prostate cancer?Yes, combining hormone drugs and radiation therapy is promising for treating prostate cancer. This combination can improve survival rates and reduce cancer recurrence compared to using radiation therapy alone. Hormone drugs help control the cancer and enhance the effectiveness of radiation therapy.12349
What safety data is available for hormone and radiation therapy in prostate cancer treatment?The safety data for hormone and radiation therapy in prostate cancer treatment includes several findings: Abiraterone acetate, used with prednisone, can cause endocrine side effects such as mineralocorticoid excess and secondary adrenal insufficiency. It also has potential cardiac risks, including atrial tachyarrhythmia and heart failure. Additionally, androgen deprivation therapy (ADT) with agents like abiraterone and enzalutamide can lead to loss of skeletal muscle mass. The combination of radium-223 with abiraterone or enzalutamide has shown improved survival, but its safety profile is not fully clear.710111213
What data supports the idea that Hormone + Radiation Therapy for Prostate Cancer is an effective treatment?The available research shows that combining hormone therapy with radiation therapy can be effective for treating prostate cancer. For example, one study found that adding bicalutamide, a hormone therapy drug, to radiation therapy significantly improved overall survival in men with locally advanced prostate cancer. Another study highlighted that enzalutamide, when combined with salvage radiation therapy, helped control prostate tumor growth in men with a rising PSA after surgery. These findings suggest that hormone therapy combined with radiation can be more effective than radiation alone in certain cases.35689
Do I need to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop all current medications. However, if you are taking a 5-alpha reductase inhibitor, you must stop it before randomization, but no washout period is required. If you are entering the Intensification Cohort, you must discontinue or substitute medications that lower the seizure threshold at least 30 days before randomization. If you are on HIV or HCV medications, consult your doctor as apalutamide may interact with them.
Eligibility Criteria
Men over 18 with high-risk prostate cancer, no metastatic disease outside the pelvis, and a good performance status can join. They must have had no prior chemotherapy for prostate cancer in the last 3 years, no radical prostatectomy or pelvic radiotherapy, and not be on certain medications like 5-alpha reductase inhibitors at randomization.Inclusion Criteria
Appropriate stage for study entry based on the following diagnostic workup: History/physical examination within 120 days prior to registration; Bone imaging within 120 days prior to registration; Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative NaF PET/CT or negative Axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed). Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or NaF PET will still be eligible CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by ≥10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e. N1), but whose nodes do not meet traditional size criteria for positivity (i.e. they measure ≥ 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study Age ≥ 18 Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration) Platelet count ≥ -100 x 10^3/uL independent of transfusion and/or growth factors (within 120 days prior to registration) Creatinine clearance (CrCl) ≥ 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration) For Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility Either a CrCl ≥ 30 ml/min or calculated glomerular filtration rate (GFR) ≥ 30 will make a patient eligible Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 120 days prior to registration) Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject is eligible Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN (within 120 days prior to registration) Serum albumin ≥ 3.0 g/dL (within 120 days prior to registration) The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count ≥ 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with apalutamide For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator The patient or a legally authorized representative must provide study-specific informed consent prior to study entry Confirmation of Decipher score
My prostate cancer is aggressive (Gleason score 8-10).
My cancer has spread to my lymph nodes, which are enlarged.
My cancer is classified as stage T3a to T4 based on exams or imaging.
Treatment Details
The trial is testing less intense vs usual hormone therapy plus radiation for patients with low gene risk scores. For those with high gene risk scores, it's comparing more intense treatment (adding apalutamide) to usual care. The goal is to see if these approaches control cancer better without spreading.
4Treatment groups
Experimental Treatment
Active Control
Group I: Arm IV (intensification study)Experimental Treatment10 Interventions
Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin) for 24 months in the absence of disease progression or unacceptable toxicity. Patients also receive apalutamide PO QD. Treatment repeats every 90 days for up to 8 cycles (24 months) in the absence of disease progression or unacceptable toxicity.
Group II: Arm II (de-intensification study)Experimental Treatment11 Interventions
Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 12 months in the absence of disease progression or unacceptable toxicity.
Group III: Arm I (de-intensification study)Active Control11 Interventions
Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.
Group IV: Arm III (intensification study)Active Control11 Interventions
Patients undergo RT over 2-11 weeks and receive ADT as in Arm I.
Abiraterone Acetate is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Zytiga for:
- Metastatic castration-resistant prostate cancer
- Metastatic high-risk castration-sensitive prostate cancer
🇪🇺 Approved in European Union as Zytiga for:
- Metastatic castration-resistant prostate cancer
- Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer
🇨🇦 Approved in Canada as Zytiga for:
- Metastatic castration-resistant prostate cancer
- Metastatic castration-sensitive prostate cancer
🇯🇵 Approved in Japan as Zytiga for:
- Prostate cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
Adams Cancer CenterGettysburg, PA
UPMC Pinnacle West ShoreMechanicsburg, PA
University of Colorado HospitalAurora, CO
Rhode Island HospitalProvidence, RI
More Trial Locations
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Who is running the clinical trial?
NRG OncologyLead Sponsor
National Cancer Institute (NCI)Collaborator
References
[The combined radiation and hormonal therapy of prostatic carcinoma: a conceptual analysis]. [2006]The concept of a combination of radiotherapy and hormonal therapy for the treatment of locally advanced carcinoma of the prostate was evaluated in view of an improved success rate compared to radiotherapy alone. At present, however, radiotherapy still remains the central mode of therapy in the treatment of the local tumor. The time sequence in a combination with hormonal therapy is of importance. Antecedent hormonal treatment can reduce tumor size, thus improving local conditions for percutaneous--and especially interstitial--radiotherapy; it is indicated in patients with voiding problems. An improvement in survival rates has so far not been achieved, however, local tumor remission rates are better. With concomitant hormonal therapy, compared to radiotherapy alone, tumor progression rates are lower. It remains to be seen, whether these results can be improved by using newer pharmacological ways of androgen blockade. The application of androgen withdrawal as a secondary measure with local tumor persistence or progression after radiotherapy remains a palliative treatment of limited efficacy. Due to the heterogeneity of the available study reports and the concurrent lack of controlled, randomized trials, a conclusive evaluation of the concept of combined radio- and hormonal therapy of prostatic cancer is as yet not possible.
The effectiveness of combining hormone therapy and radiotherapy in the treatment of prostate cancer. [2019]Hormone therapy is commonly used for many patients with prostate cancer. Radiotherapy occupies a prominent role in the treatment of locally-advanced, localised, and postsurgical prostate cancer. Hormone therapy and radiotherapy are often used in combination. In this article, the major features of the hormone/radiotherapy interactions are reviewed, with emphasis on the role of combination treatment for locoregional disease. The reported results suggest a biochemical survival advantage to the use of hormone therapy with radiotherapy, in virtually all settings of non-metastatic disease, with the weakest database being in the setting of low-risk, early-stage disease. Further data are needed in order to identify the optimum target population, combination of agents, and hormone duration, as a function of patient and disease factors.
The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer. [2018]Castration therapy adjuvant to radiotherapy can significantly improve overall survival compared with radiotherapy alone in patients with locally advanced prostate cancer. Although many of the adverse effects of castration therapy are manageable, they can have a detrimental effect on quality of life. Here we evaluate the efficacy and tolerability of the non-castration-based therapy bicalutamide ('Casodex') 150 mg adjuvant to radiotherapy in patients with T1-4, M0, any n prostate cancer.
[What's new in 2009 in prostate cancer: highlights from ASTRO, EAU, ASCO and AUA meetings]. [2010]In 2009, prostate cancer was the subject of a large number of communications in international urologic, oncologic and radiation therapy conferences. The most interesting studies that are likely to modify physician's daily practice were selected. This year the results from the European (ERSPC) and the American (PLCO) mass screening studies. Many abstract on prevention, natural history and tumor markers such as PCa3 and fusion gene TMPRSS2 : ERG were presented. Adjuvant hormonal treatment was evaluated in high-risk patients. Hormonal and radiation therapy association reduces recurrence, specific and overall mortality in locally advanced prostate cancer. Intermittent hormonal treatment is an option in hormone sensitive metastatic patients. toremifene and denosumab were evaluated in the prevention of fracture risk in patients under androgen deprivation therapy. The mechanism of tumor proliferation in castrate resistant prostate cancer further explained and 2 new molecules abiraterone and MDV 3100 were presented.
Stereotactic body radiation therapy for the treatment of oligoprogression on androgen receptor targeted therapy in castration-resistant prostate cancer. [2020]Castration-resistant prostate cancer is an incurable disease. To date, six agents-abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T- have shown clinical efficacy in phase III clinical trials, leading to their FDA approval. Patients are typically sequenced through most or all of these agents, and then eventually succumb to their disease. Development of new treatments remains an unmet need. We report a case of a patient who progressed on enzalutamide with a single enlarging metastatic lesion, was treated with ablative stereotactic body radiation therapy while maintaining the same systemic treatment, who then had durable complete remission. Our findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.
Combined abiraterone acetate plus prednisone, salvage prostate bed radiotherapy and LH-RH agonists (CARLHA-GEP12) in biochemically-relapsing prostate cancer patients following prostatectomy: A phase I study of the GETUG/GEP. [2022]To establish the maximum tolerated dose of abiraterone acetate plus prednisone (AA) combined with salvage radiotherapy (SRT) and goserelin in a phase 1 study in men with rising PSA following radical prostatectomy.
Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. [2022]Abiraterone acetate is a highly variable drug and has been approved for the treatment of patients with metastatic castration-resistant prostate cancer in many countries. This study was conducted to compare the pharmacokinetic profile between the test product (abiraterone acetate tablet) and reference product ZYTIGA® (250 mg) mainly.
Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial. [2020]Abiraterone acetate plus prednisone or prednisolone improves progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer. Radium-223 improves overall survival and delays the onset of symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases. We assessed concurrent treatment with abiraterone acetate plus prednisone or prednisolone and radium-223 in such patients.
A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA). [2021]In men with a rising PSA following radical prostatectomy, salvage radiation therapy (SRT) offers a second chance for cure. Hormonal therapy can be combined with SRT in order to increase prostate tumor control, albeit with associated higher rates of treatment side effects. This trial studies the effectiveness of SRT combined with hormonal therapy using a more potent anti-androgen with a favorable side effect profile. Enzalutamide, a next generation selective androgen receptor antagonist, is approved by the Food and Drug Administration for the treatment of metastatic castrate-resistant prostate cancer (CRPC) where it has been shown to improve overall survival in combination with androgen deprivation therapy. The primary objective of this study is to evaluate the efficacy of combination SRT and enzalutamide for freedom-from-PSA-progression. Secondary objectives include time to local recurrence within the radiation field, metastasis-free survival and safety as determined by frequency and severity of adverse events.
Heart failure and atrial tachyarrhythmia on abiraterone: A pharmacovigilance study. [2021]Abiraterone and enzalutamide are recently-approved androgen deprivation therapies (ADTs) for metastatic prostate cancer, with unknown cardiac safety profiles. Abiraterone has a propensity to hypermineralocorticism on top of androgen deprivation, so might carry an additional risk for atrial tachyarrhythmia (AT) and heart failure (HF) compared with other ADTs.
A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer. [2021]Radium-223, abiraterone, and enzalutamide have each been shown to significantly improve survival as monotherapy in patients with metastatic castration-resistant prostate cancer. However, effects of combination radium-223 plus abiraterone or enzalutamide on survival and safety remain unclear.
A comparison of the sarcopenic effect of androgen receptor-axis-targeted agents vs. androgen deprivation alone in patients with metastatic prostate cancer. [2023]Androgen deprivation therapy (ADT) with androgen receptor axis-targeted (ARAT) therapy is the standard of care provided to patients with metastatic prostate cancer. While effective, it results in sequelae, such as loss of skeletal muscle mass. In this study, we compared the sarcopenic effects of abiraterone and enzalutamide, two ARATs used to treat metastatic prostate cancer.
Abiraterone-Induced Endocrinopathies. [2023]Abiraterone, a CYP17A1 inhibitor, is used along with prednisone in patients with castration-resistant and castration-sensitive prostate cancer, yielding improved overall and disease-free survival. However, little is documented in the endocrinology literature about the incidences of the endocrine side effects of abiraterone. In this case series, we discuss the diagnosis and management of 3 prostate cancer patients who experienced mineralocorticoid excess and secondary adrenal insufficiency related to abiraterone and prednisone use.