Clinical Trials /

Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer

NCT03902951

Description:

This phase II trial studies how well antiandrogen therapy (leuprolide, apalutamide, and abiraterone acetate) and stereotactic body radiation therapy (SBRT) works in treating patients with prostate cancer that has come back and has spread to other parts of the body. Drugs used in chemotherapy, such as leuprolide, apalutamide, and abiraterone acetate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving antiandrogen therapy and SBRT may work better in treating patients with prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer
  • Official Title: A Single-Arm, Open-Label, Phase II Study of Systemic and Tumor Directed Therapy for Recurrent Oligometastatic M1 Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-001037
  • SECONDARY ID: NCI-2019-00337
  • SECONDARY ID: 18-001037
  • SECONDARY ID: P30CA016042
  • NCT ID: NCT03902951

Conditions

  • Metastatic Prostate Adenocarcinoma
  • Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation
  • Recurrent Prostate Carcinoma
  • Stage IVB Prostate Cancer AJCC v8

Interventions

DrugSynonymsArms
Abiraterone AcetateCB7630, ZytigaTreatment (leuprolide, apalutamide, abiraterone acetate, SBRT)
ApalutamideARN 509, ARN-509, ARN509, JNJ 56021927, JNJ-56021927Treatment (leuprolide, apalutamide, abiraterone acetate, SBRT)
Leuprolide AcetateA-43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Procren, Procrin, Prostap, TAP-144, Trenantone, Uno-Enantone, ViadurTreatment (leuprolide, apalutamide, abiraterone acetate, SBRT)

Purpose

This phase II trial studies how well antiandrogen therapy (leuprolide, apalutamide, and abiraterone acetate) and stereotactic body radiation therapy (SBRT) works in treating patients with prostate cancer that has come back and has spread to other parts of the body. Drugs used in chemotherapy, such as leuprolide, apalutamide, and abiraterone acetate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving antiandrogen therapy and SBRT may work better in treating patients with prostate cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the efficacy of combined systemic and tumor directed therapy for recurrent
      oligometastatic M1a,b prostate cancer patients with 1-5 metastases (exclusive of pelvic nodal
      N1 metastases) staged by prostate-specific membrane antigen (PSMA) positron emission
      tomography (PET)-computed tomography (CT).

      SECONDARY OBJECTIVES:

      I. Time to biochemical progression. II. Time to additional antineoplastic therapy. III.
      Prostate cancer specific survival. IV. Safety and tolerability. V. Assessment of health
      related quality of life using the Functional Assessment of Cancer Therapy - Prostate (FACT-P)
      scale.

      CORRELATIVE OBJECTIVES:

      I. To determine genomic and transcriptomic features present in metastatic tumors in patients
      that respond to this multimodal therapy.

      II. To evaluate biomarkers of response using circulating tumor cells (CTCs). III. To evaluate
      biomarkers of response using circulating tumor deoxyribonucleic acid (DNA) (ctDNA).

      IV. To evaluate immunophenotypes of circulating immune cells.

      OUTLINE:

      Patients receive a single dose of leuprolide subcutaneously (SC) on day 1 and apalutamide
      orally (PO) once daily (QD) and abiraterone acetate PO QD for up to 6 months in the absence
      of disease progression or unacceptable toxicity. Beginning 2 months of initiation of
      antiandrogen therapy (ADT), patients also receive SBRT over 1, 3, or 5 fractions in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up within 2 -4 weeks, every 30
      days for 6 months, and then every 3 months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (leuprolide, apalutamide, abiraterone acetate, SBRT)ExperimentalPatients receive leuprolide SC on day 1, Patients receive a single dose of leuprolide SC on day 1 and apalutamide PO QD and abiraterone acetate PO QD for up to 6 months in the absence of disease progression or unacceptable toxicity. Beginning 2 months of initiation of ADT, patients also receive SBRT over 1, 3, or 5 fractions in the absence of disease progression or unacceptable toxicity.
  • Abiraterone Acetate
  • Apalutamide
  • Leuprolide Acetate

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of prostate adenocarcinoma after radical prostatectomy (primary
             small cell carcinoma of the prostate is not allowed, however adenocarcinoma with
             neuroendocrine differentiation is allowed)

          -  Presence of 1-5 visible metastases (by PSMA PET-CT)

               -  At least one metastasis must be M1a-b

               -  Visceral metastases are not allowed

               -  Patients may have any number of pelvic nodal metastases (but largest must be < 2
                  cm)

               -  Metastases must be amenable to treatment with SBRT

               -  Biopsy of one metastasis must be attempted, unless unsafe to perform

          -  Patient must be fit to undergo SBRT to all visible sites of metastases, ADT

          -  Total testosterone > 150 ng/dL prior to ADT (optimal time to measure total
             testosterone is between 8 and 9 am)

          -  Adequate performance status (Eastern Cooperative Oncology Group [ECOG] 0-1)

          -  Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors within 3
             months prior to randomization

          -  Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors
             within 3 months prior to randomization

          -  Serum albumin >= 3.0 g/dL

          -  Glomerular filtration rate (GFR) >= 45 mL/min

          -  Serum potassium >= 3.5 mmol/L

          -  Serum total bilirubin =< 1.5 x upper limits of normal (ULN)

               -  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 may be eligible

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN

          -  Medications known to lower the seizure threshold must be discontinued or substituted
             at least 4 weeks prior to study entry

        Exclusion Criteria:

          -  Any evidence of spinal cord compression (radiological or clinical)

          -  Prior pelvic malignancy

          -  Prior pelvic radiation aside from salvage prostate radiation

          -  Concurrent malignancy aside from superficial skin cancers or superficial bladder
             tumors

          -  Inability to undergo radiotherapy, or ADT

          -  Primary small cell carcinoma of the prostate (prostate adenocarcinoma with
             neuroendocrine differentiation is allowed)

          -  Inflammatory bowel disease or active collagen vascular disease

          -  History of any of the following:

               -  Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke
                  within 1 year to randomization, brain arteriovenous malformation, Schwannoma,
                  meningioma, or other benign central nervous system [CNS] or meningeal disease
                  which may require treatment with surgery or radiation therapy)

               -  Severe or unstable angina, myocardial infarction, symptomatic congestive heart
                  failure, arterial or venous thromboembolic events (eg, pulmonary embolism,
                  cerebrovascular accident including transient ischemic attacks), or clinically
                  significant ventricular arrhythmias within 6 months prior to randomization

          -  Current evidence of any of the following:

               -  Uncontrolled hypertension

               -  Gastrointestinal disorder affecting absorption

               -  Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)

               -  Any chronic medical condition requiring a higher dose of corticosteroid than 10
                  mg prednisone/prednisolone once daily

               -  Any condition that in the opinion of the investigator would preclude
                  participation in this study

               -  Concomitant strong CYP3A4 inducers. (If a strong CYP3A4 inducer must be
                  co-administered, abiraterone acetate dose frequency will be adjusted). [SAFETY:
                  Warning against use with CYP2C8 inhibitors with narrow therapeutic index is also
                  pertinent to be included as it is also part of United States Prescribing
                  Information (USPI): In a CYP2C8 drug-drug interaction trial in healthy subjects,
                  the area under curve (AUC) of pioglitazone (CYP2C8 substrate) was increased by
                  46% when pioglitazone was given together with a single dose of 1,000 mg
                  abiraterone acetate. Therefore, patients should be monitored closely for signs of
                  toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used
                  concomitantly with ZYTIGA]

               -  Treatment with CYP2D6 substrates that have a narrow therapeutic index. If an
                  alternative treatment cannot be used, a dose reduction of the CYP2D6 substrate
                  may be considered

               -  Baseline moderate and severe hepatic impairment (ChildPugh Class B & C)

          -  Presence of visceral metastases (i.e., stage M1c)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percent of patients achieving a serum prostate specific antigen (PSA) of < 0.05 ng/mL
Time Frame:Up to 6 months post treatment
Safety Issue:
Description:Will be summarized by count and percent along with the 95% confidence interval.

Secondary Outcome Measures

Measure:Time to biochemical progression
Time Frame:Baseline to first rise in PSA to 0.2 ng/mL, assessed up to 2 years
Safety Issue:
Description:Will be summarized using Kaplan-Meier method.
Measure:Time to radiographic progression
Time Frame:Baseline to time when any imaging shows new evidence of metastatic disease, assessed up to 2 years
Safety Issue:
Description:Will be summarized using Kaplan-Meier method.
Measure:Time to initiation of alternative antineoplastic therapy
Time Frame:Baseline to time when new anti-prostate cancer therapy is initiated, assessed up to 2 years
Safety Issue:
Description:Will be summarized using Kaplan-Meier method.
Measure:Prostate cancer specific survival
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:
Measure:Health related quality of life: Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale - patient questionnaire
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:This uses the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire. It assesses patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Items are rated on a 0 to 4 Likert type scale and combined to produce subscale scores for each domain and a global score, the higher the score, the better the quality of life. Range from 0-150 . Data will be aggregated per patient and over time.
Measure:Incidence of adverse events
Time Frame:Up to 30 days post treatment
Safety Issue:
Description:The intensity of clinical adverse events will be graded according to the Common Terminology Criteria for Adverse Events version (v) 4.0 (CTCAE) grading system in the toxicity categories.
Measure:Biomarker analysis
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:Will conduct whole exome deep sequencing (WES), RNA sequencing (RNA-seq), and comparative genomic hybridizations (CGH) of the metastatic tumors.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jonsson Comprehensive Cancer Center

Last Updated

November 7, 2019