Hormone Therapy and Intensity-Modulated Radiation Therapy in Treating Patients With Metastatic Prostate Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well hormone therapy and intensity-modulated radiation therapy work in treating patients with prostate cancer that has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Anti-hormone therapy using goserelin, leuprolide acetate, or bicalutamide, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving hormone therapy and intensity-modulated radiation therapy may work better in treating patients with prostate cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the time to prostate-specific antigen (PSA) relapse in patients with oligometastatic (=< 5 lesions) hormone-sensitive prostate cancer treated with 36 weeks of androgen deprivation therapy and localized radiotherapy to all known tumor sites. II. To assess the prostate-specific-antigen (PSA) and objective response rate to treatment with 36 weeks of androgen deprivation and localized radiotherapy in patients with oligometastatic hormone-sensitive prostate cancer. III. To assess the toxicity of 36 weeks of androgen deprivation and localized radiation therapy to oligometastases in patients with oligometastatic hormone-sensitive prostate cancer. IV. In appropriate situations evaluate the feasibility and toxicities of using helical tomotherapy image-guided intensity-modulated radiation therapy (IMRT) to treat oligometastatic sites. OUTLINE: ANDROGEN DEPRIVATION THERAPY (ADT): Patients not currently on ADT receive goserelin acetate subcutaneously (SC) or leuprolide acetate via injection once every 4 or 12 weeks and bicalutamide orally (PO) once daily (QD). Treatment repeats every 12 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients already receiving ADT at the time of enrollment continue treatment until they have received 36 weeks of therapy. RADIATION THERAPY: Patients achieving PSA normalization after initiation of androgen deprivation therapy undergo intensity-modulated radiation therapy daily for 2-7 weeks during or after completion of androgen deprivation therapy. After completion of study treatment, patients are followed up every 4 weeks for 2 years, then every 3 months after year 2, and then every 6 months thereafter.

Official Title
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Androgen Deprivation and Localized Radiotherapy to Metastases in Patients With Oligometastatic Hormone - Sensitive Prostate Cancer

Conditions
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PSA Level Greater Than Two, Stage IV Prostate Adenocarcinoma AJCC v7

Intervention / Treatment
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* Drug: Bicalutamide
* Drug: Goserelin Acetate
* Radiation: Intensity-Modulated Radiation Therapy
* Other: Laboratory Biomarker Analysis
* Drug: Leuprolide Acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically proven diagnosis of adenocarcinoma of the prostate stage N1, N2, N3, M1a, M1b, M1c with =< 5 metastatic lesions; if the diagnosis of metastasis in the lymph node is based solely on imaging computed tomography (CT) scan or magnetic resonance imaging (MRI), the longitudinal diameter of the lymph node has to be >= 2.0 cm; if the lymph node is positive on positron emission tomography (PET) or ProstaScint scan, the longitudinal diameter of the lymph node on CT scan or MRI has to be >= 1.5 cm Patients who have measurable disease must have had X-rays, scans or physical examination used for tumor measurement completed within 28 days prior to registration; patients must have non-measurable disease assessed within 42 days prior to registration Patients must have had documented PSA of > 2 prior to onset of androgen deprivation Patients might have received up to 36 weeks of adjuvant androgen deprivation therapy and up to 36 weeks of androgen deprivation therapy for metastatic disease prior to enrollment to this study; patients may be on androgen deprivation for metastatic disease at the time of enrollment to the protocol; adjuvant therapy must have been completed at least 2 years before androgen deprivation for metastatic disease and patients must remain hormone sensitive Prior radiation therapy for metastatic disease is not allowed Prior chemotherapy for metastatic disease is not allowed; prior neoadjuvant and adjuvant chemotherapy is allowed; patients must have recovered from all acute side-effects related to previous systemic therapy Patients are allowed to receive one prior systemic non-chemotherapeutic treatment (i. e. immunotherapy, receptor tyrosine kinase inhibitor, antiangiogenic agent, differentiation agent) for recurrent or metastatic disease; patients must have recovered from all acute side-effects related to previous systemic therapy Use of bisphosphonates is allowed at the discretion of treating physician Patients must be capable of understanding the nature of the trial and must give written informed consent Patients must have a World Health Organization (WHO) performance status of 0, 1, or 2 Exclusion Criteria: Patients with unstable or severe intercurrent medical conditions or active, uncontrolled infection Patients with a history of orchiectomy Patients undergoing therapy with other investigational agents; patients must have recovered from all acute effects of previously administered investigational agents and sufficient time must have elapsed since last administration to ensure the drug interactions not occur during this study Patients with a history of brain metastases or who currently have treated or untreated brain metastases Patients who have demonstrated refractoriness to hormone therapy with luteinizing hormone-releasing hormone (LHRH) agonist; refractoriness is defined as occurrence of one of the following while on therapy with LHRH agonist: increase in PSA by 25% over baseline (to at least > 2 ng/ml) on two consecutive PSA measurements, 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, clear worsening of any non-measurable disease, reappearance of any lesion that had disappeared, appearance of any new lesion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (androgen therapy, radiation therapy)<br>ADT: Patients not currently on ADT receive goserelin acetate SC or leuprolide acetate via injection once every 4 or 12 weeks and bicalutamide PO QD. Treatment repeats every 12 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients already receiving ADT at the time of enrollment continue treatment until they have received 36 weeks of therapy. RADIATION THERAPY: Patients achieving PSA normalization after initiation of androgen deprivation therapy undergo intensity-modulated radiation therapy daily for 2-7 weeks during or after completion of androgen deprivation therapy. | Drug: Bicalutamide<br>* Given PO<br>* Other names: ICI 176334;Drug: Goserelin Acetate<br>* Given SC<br>* Other names: Zoladex;Radiation: Intensity-Modulated Radiation Therapy<br>* Undergo IMRT<br>* Other names: Intensity-Modulated Radiotherapy;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Leuprolide Acetate<br>* Given via injection<br>* Other names: Viadur;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Prostate-specific Antigen (PSA) Relapse | Time from the date of the last dose of bicalutamide or the last day of radiation therapy (whichever comes later) until the date criteria are met for PSA relapse. PSA relapse after completion of initial 36 weeks of androgen deprivation therapy is defined as an increase in PSA value to above pre-therapy level, or to > 10, whichever is smaller. For example, a patient with pre-treatment PSA level of 40 will resume androgen deprivation therapy when PSA level is > 10, while a patient with pre-treatment PSA level of 3 will resume androgen deprivation therapy when PSA level is > 3. | End-of-therapy until PSA reached pre-treatment level or 10 (whichever was lower) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients Who Achieved PSA Nadir of < 0.2 at 36 Weeks. | Number of Patients who achieved PSA nadir of < 0.2 at 36 weeks. | During the time period between on-study PSA to off-study PSA, up to 36 weeks. | 
| Rate of Treatment Failure (no PSA Threshold Below 4 ng/dl, or no PSA Below Baseline Level Before LHRH Treatment). | Treatment failures: Count and percent of patients NOT reaching PSA concentration in serum either below 4 ng/dl or below baseline before LHRH treatment . | Off-treatment PSA measurement date minus on-study PSA measurement date, up to 36 weeks. | 
| Length of Follow-up | Length of follow-up in weeks to off-study date. Patients are treated for 36 weeks (+/- 2 weeks) with androgen deprivation therapy. Patients are evaluated for disease on day 1 of each of three 12-week cycles. After the last cycle of anti-androgen therapy, patients are assessed every four weeks until PSA relapse occurs, up to 264.8 weeks (61.4 months; 5.1 years). Patients will remain off-treatment until they meet the criteria for re-treatment with androgen deprivation therapy, whereupon they will be taken off of the protocol. After patients are taken off protocol, we will do a chart review for long-term outcomes. | Patients are evaluated for disease on day 1 of each of three 12-week cycles. After the last cycle of anti-androgen therapy, patients are assessed every four weeks until PSA relapse occurs, up to 61.4 months | 
| Count of Patients Remaining Off of Therapy | Patients who remained off of therapy, in remission, out of the number of patients with metastases limited to pelvic lymph nodes. | after 36 week LHRH treatment window. | 
| Follow-up of the 8 Patients With Metastases Limited to Pelvic Lymph Nodes. | Length of follow-up of the 8 patients with metastases limited to pelvic lymph nodes, months. Patients are followed on day one of each of three 12-week periods. After completion of therapy, patients are followed every four weeks until PSA relapse, up to 46.4 months. | Patients are followed on day one of each of three 12-week periods. After completion of therapy, patients are followed every four weeks until PSA relapse, up to 46.4 months. | 
| CR Without ADT in Patients With Metastases Limited to Pelvic Lymph Nodes. | Number of patients remaining in complete remission without androgen deprivation therapy in patients with metastases limited to pelvic lymph nodes. | after 36 weeks of LHRH therapy. |