Hormone + Radiation Therapy for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+599 other locations
Overseen byPaul L Nguyen
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: NRG Oncology
Must be taking: Hormone therapy
Must not be taking: 5-alpha reductase inhibitors
Disqualifiers: Metastatic disease, Seizure disorder, others
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.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop all current medications, but if you are taking a 5-alpha reductase inhibitor, you should stop it before randomization. Additionally, if you are in the Intensification Cohort, you must stop or substitute medications that lower the seizure threshold at least 30 days before randomization.
What data supports the effectiveness of the treatment involving hormone and radiation therapy for prostate cancer?
Research shows that combining hormone therapy with radiation can improve prostate cancer control. For instance, adding bicalutamide to radiotherapy significantly improves survival in locally advanced prostate cancer. Additionally, abiraterone acetate with prednisone has been shown to improve survival in metastatic cases.12345
Is hormone and radiation therapy for prostate cancer safe for humans?
How does the hormone and radiation therapy treatment for prostate cancer differ from other treatments?
This treatment combines hormone therapy with radiation therapy, using a variety of drugs like Abiraterone Acetate and Apalutamide, which are known for their effectiveness in blocking androgens (male hormones) that fuel prostate cancer growth. The combination aims to improve tumor control and survival rates compared to radiation alone, although it may come with more side effects.25111213
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
High-risk disease defined as having at least one or more of the following: PSA > 20 ng/mL prior to starting ADT Note: Patients receiving a 5-alpha reductase inhibitor (ex. finasteride) at the time of enrollment are eligible. The baseline PSA value should be doubled for PSAs taken while on 5-alpha reductase inhibitors and the medication should be discontinued prior to randomization but a washout period is not required. cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.]) Gleason score of 8-10 Node positive by conventional imaging with a short axis of at least 1.0 cm
My prostate cancer is aggressive (Gleason score 8-10).
My cancer has spread to my lymph nodes, which are enlarged.
See 6 more
Exclusion Criteria
Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e. bone scan, CT scan, MRI) Prior systemic chemotherapy within ≤ 3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration Prior radical prostatectomy Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields Current use of 5-alpha reductase inhibitor. NOTE: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible History of any of the following: Seizure disorder Current severe or unstable angina New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.) History of any condition that in the opinion of the investigator, would preclude participation in this study Evidence of any of the following at registration: Active uncontrolled infection requiring IV antibiotics Baseline severe hepatic impairment (Child Pugh Class C) Inability to swallow oral pills Any current condition that in the opinion of the investigator, would preclude participation in this study Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone-releasing hormone [LHRH] agonist and oral anti-androgen) is ≤ 60 days prior to registration; Please note: baseline PSA must be obtained prior to the start of any ADT PRIOR TO STEP 2 RANDOMIZATION: Evidence of known gastrointestinal disorder affecting absorption of oral medications at registration For patients entering the Intensification Cohort ONLY: Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥ 160 mmHg or diastolic BP ≥ 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants undergo radiation therapy over 2-11 weeks and receive androgen deprivation therapy (ADT) for 12 or 24 months, with or without apalutamide, depending on genomic risk score.
24 months
Regular visits as clinically indicated
Follow-up
Participants are monitored for safety and effectiveness after treatment, including imaging and blood sample collection.
Up to 13 years
Periodic visits as clinically indicated
Treatment Details
Interventions
- Abiraterone Acetate (Hormone Therapy)
- Apalutamide (Androgen Receptor Antagonist)
- Bicalutamide (Hormone Therapy)
- Buserelin (Hormone Therapy)
- Degarelix (Hormone Therapy)
- Flutamide (Hormone Therapy)
- Goserelin (Hormone Therapy)
- Histrelin (Hormone Therapy)
- Leuprolide (Hormone Therapy)
- Prednisone (Hormone Therapy)
- Radiation Therapy (Radiation)
- Triptorelin (Hormone Therapy)
Trial OverviewThe 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.
Participant Groups
4Treatment groups
Experimental Treatment
Active Control
Group I: Arm IV (intensification study)Experimental Treatment16 Interventions
Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix) 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. Patients undergo bone scan, PET scan, CT scan, and MRI at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.
Group II: Arm II (de-intensification study)Experimental Treatment17 Interventions
Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo bone scan, PET scan, CT scan, and MRI at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.
Group III: Arm I (de-intensification study)Active Control17 Interventions
Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity. Patients undergo bone scan, PET scan, CT scan, and MRI at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.
Group IV: Arm III (intensification study)Active Control17 Interventions
Patients undergo RT over 2-11 weeks and receive ADT as in Arm I. Patients undergo bone scan, PET scan, CT scan, and MRI at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.
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
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.
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.
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.
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.
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.
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 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.
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.
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.
[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.
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 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.