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

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ClinicalTrials.gov Identifier: NCT03902951
Recruitment Status : Not yet recruiting
First Posted : April 4, 2019
Last Update Posted : April 4, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Prostate Adenocarcinoma Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation Recurrent Prostate Carcinoma Stage IVB Prostate Cancer AJCC v8 Drug: Abiraterone Acetate Drug: Apalutamide Drug: Leuprolide Acetate Other: Quality-of-Life Assessment Other: Questionnaire Administration Radiation: Stereotactic Body Radiation Therapy Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm, Open-Label, Phase II Study of Systemic and Tumor Directed Therapy for Recurrent Oligometastatic M1 Prostate Cancer
Estimated Study Start Date : May 1, 2019
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : March 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Treatment (leuprolide, apalutamide, abiraterone acetate, SBRT)
Patients 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.
Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Zytiga

Drug: Apalutamide
Given PO
Other Names:
  • ARN 509
  • ARN-509
  • ARN509
  • JNJ 56021927
  • JNJ-56021927

Drug: Leuprolide Acetate
Given SC
Other Names:
  • A-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
  • Viadur

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT
Other Names:
  • SABR
  • SBRT
  • Stereotactic Ablative Body Radiation Therapy




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


Secondary Outcome Measures :
  1. Time to biochemical progression [ Time Frame: Baseline to first rise in PSA to 0.2 ng/mL, assessed up to 2 years ]
    Will be summarized using Kaplan-Meier method.

  2. Time to radiographic progression [ Time Frame: Baseline to time when any imaging shows new evidence of metastatic disease, assessed up to 2 years ]
    Will be summarized using Kaplan-Meier method.

  3. 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 ]
    Will be summarized using Kaplan-Meier method.

  4. Prostate cancer specific survival [ Time Frame: Up to 2 years post treatment ]
  5. Health related quality of life [ Time Frame: Up to 2 years post treatment ]
    Will be assessed using the Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale.

  6. Incidence of adverse events [ Time Frame: Up to 30 days post treatment ]
    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.

  7. Biomarker analysis [ Time Frame: Up to 2 years post treatment ]
    Will conduct whole exome deep sequencing (WES), RNA sequencing (RNA-seq), and comparative genomic hybridizations (CGH) of the metastatic tumors.


Other Outcome Measures:
  1. Genomic and transcriptomic features present in metastatic tumors [ Time Frame: Up to 2 years post treatment ]
    Will conduct whole exome deep sequencing (WES), ribonucleic acid (RNA) sequencing (RNA-seq), and comparative genomic hybridizations (CGH) of the metastatic tumors of the 28 patients enrolled in the Phase II trial. Then, will identify discriminating features of the metastatic tumors in responders that distinguish them from the non-responders.

  2. Circulating tumor deoxyribonucleic acid (ctDNA) for predictors of response [ Time Frame: Up to 2 years post treatment ]
  3. Circulating tumor cells (CTCs) for predictors of response [ Time Frame: Up to 2 years post treatment ]
  4. Changes in circulating immunophenotypes [ Time Frame: Baseline up to 2 years post treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03902951


Locations
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United States, California
UCLA / Jonsson Comprehensive Cancer Center Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Nicholas Nickols    310-825-8278    nnickols@mednet.ucla.edu   
Principal Investigator: Nicholas Nickols         
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Nicholas Nickols UCLA / Jonsson Comprehensive Cancer Center

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Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03902951     History of Changes
Other Study ID Numbers: 18-001037
NCI-2019-00337 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
18-001037 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center )
P30CA016042 ( U.S. NIH Grant/Contract )
First Posted: April 4, 2019    Key Record Dates
Last Update Posted: April 4, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Genital Diseases, Male
Carcinoma
Abiraterone Acetate
Leuprolide
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 Enzyme Inhibitors
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal