Radium Ra 223 Dichloride, Hormone Therapy and Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Prostate Cancer

Sponsor

City of Hope Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03361735

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase 2 trial studies radium Ra 223 dichloride, hormone therapy and stereotactic body radiation in treating patients with prostate cancer that has spread to other places in the body. Radium Ra 223 dichloride contains a radioactive substance that collects in the bone and gives off radiation that may kill cancer cells. Hormone therapy using leuprolide acetate or goserelin acetate may fight prostate cancer by lowering the amount of testosterone the body makes. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Giving radium Ra 223 dichloride, hormone therapy and stereotactic body radiation may work better at treating prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Adenocarcinoma	Drug: Leuprolide Acetate Drug: Goserelin Acetate Radiation: Stereotactic Body Radiation Therapy Radiation: Radium Ra 223 Dichloride Other: Laboratory Biomarker Analysis Drug: Degarelix	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

To assess the time to treatment failure (TTF) in patients who initiated the protocol regimen of androgen deprivation therapy (ADT) with stereotactic body radiation therapy (SBRT) and radium Ra 223 dichloride and received at least one dose with radium Ra 223 dichloride.

SECONDARY OBJECTIVES:

To assess the safety of adding radium Ra 223 dichloride to SBRT and ADT in patients with oligometastatic castration sensitive prostate cancer.
To assess the prostate-specific antigen (PSA) and overall response rate (ORR) after 6 cycles of radium Ra 223 dichloride (cycle 8 day 1).
To assess the progression-free survival (PFS) in patients with oligometastatic castration sensitive prostate cancer who initiated the protocol regimen of ADT with SBRT and radium Ra 223 dichloride and received at least one dose of radium Ra 223 dichloride.
To assess time to bone specific PFS in patients with oligometastatic castration sensitive prostate cancer who initiated the protocol regimen of ADT with SBRT and radium Ra 223 dichloride and received at least one dose of radium Ra 223 dichloride.
To assess overall survival, complete response rate, duration of response, and duration of overall complete response and duration of stable disease in patients with oligometastatic castration sensitive prostate cancer who initiated the protocol regimen of ADT with SBRT and radium Ra 223 dichloride.
To assess long-term toxicities during 5-year follow-up in patients with oligometastatic castration sensitive prostate cancer who initiated the protocol regimen of ADT with SBRT and radium Ra 223 dichloride and received at least one dose of radium Ra 223 dichloride.

TERTIARY OBJECTIVES:

To perform exploratory analysis of primary or metastatic tumor mutation patterns in this study population at baseline.
To identify immune system factors in the blood that change during the course of ADT-radiotherapy for metastatic prostate cancer.
To describe the rate of normalization of the total alkaline phosphatase level (defined as a return to a value within the normal range) at the end of protocol therapy in patients oligometastatic castration sensitive prostate cancer with total alkaline phosphatase values above the upper limit of the normal range at baseline.

OUTLINE:

Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, or degarelix for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride intravenously (IV) over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 5 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Trial of Radium Ra 223 Dichloride in Combination With Androgen Deprivation Therapy and Stereotactic Body Radiation Therapy for Patients With Oligometastatic Castration Sensitive Prostate Cancer

Actual Study Start Date :

Aug 29, 2018

Anticipated Primary Completion Date :

Dec 29, 2023

Anticipated Study Completion Date :

Dec 29, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (hormone therapy, SBRT, radium Ra 223 dichloride) Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride IV over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.	Drug: Leuprolide Acetate Intramuscular or subcutaneous injection Other Names: 377526 6-D-Leucine-9-(N-ethyl-L-prolinamide)-1-9-luteinizing Hormone-releasing Factor (Pig) Monoacetate 6-D-Leucine-9-(N-ethyl-L-prolinamide)-10-deglycinamide Luteinizing Hormone-Releasing Factor (Pig) Monoacetate 74381-53-6 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 Drug: Goserelin Acetate Subcutaneous injection Other Names: 606864 65807-02-5 D-Ser(bu(t))(6)azgly(10)-LHRH Acetate ZDX Zoladex Radiation: Stereotactic Body Radiation Therapy Undergo SBRT Other Names: SABR SBRT Stereotactic Ablative Body Radiation Therapy Radiation: Radium Ra 223 Dichloride Given IV Other Names: 444811-40-9 Alpharadin BAY 88-8223 BAY88-8223 Radium 223 Dichloride RADIUM CHLORIDE RA-223 Radium-223 Dichloride Xofigo Other: Laboratory Biomarker Analysis Correlative studies Drug: Degarelix Subcutaneous injection Other Names: 214766-78-6 FE200486 Firmagon

Arm

Intervention/Treatment

Experimental: Treatment (hormone therapy, SBRT, radium Ra 223 dichloride)

Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride IV over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.

Drug: Leuprolide Acetate

Intramuscular or subcutaneous injection

Other Names:

377526

6-D-Leucine-9-(N-ethyl-L-prolinamide)-1-9-luteinizing Hormone-releasing Factor (Pig) Monoacetate

6-D-Leucine-9-(N-ethyl-L-prolinamide)-10-deglycinamide Luteinizing Hormone-Releasing Factor (Pig) Monoacetate

74381-53-6

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

Drug: Goserelin Acetate

Subcutaneous injection

Other Names:

606864

65807-02-5

D-Ser(bu(t))(6)azgly(10)-LHRH Acetate

ZDX

Zoladex

Radiation: Stereotactic Body Radiation Therapy

Undergo SBRT

Other Names:

SABR

SBRT

Stereotactic Ablative Body Radiation Therapy

Radiation: Radium Ra 223 Dichloride

Given IV

Other Names:

444811-40-9

Alpharadin

BAY 88-8223

BAY88-8223

Radium 223 Dichloride

RADIUM CHLORIDE RA-223

Radium-223 Dichloride

Xofigo

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Degarelix

Subcutaneous injection

Other Names:

214766-78-6

FE200486

Firmagon

Outcome Measures

Primary Outcome Measures

Time to treatment failure [Assessed up to 5 years]
Defined as time from the initiation of androgen deprivation therapy (ADT) for metastatic disease until PSA increase to > pre-ADT level or PSA > 10 (whichever is smaller) or radiographic or clinical progression or resumption of ADT by physician's choice.
Objective response rate [Up to 5 years]
Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria. Proportion of patients achieving complete response (CR) or partial response (PR) at course 8, day 1 (post 6 doses of radium Ra 223 dichloride).

Secondary Outcome Measures

Progression-free survival [From the initiation of ADT for metastatic disease until PSA progression or radiographic progression or death, assessed up to 5 years]
Progression will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Overall survival [From date of initiation of protocol treatment to date of death from any cause, assessed up to 5 years]
Complete response (CR) rate defined as the proportion of patients achieving CR [Up to 5 years]
Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Duration of response [From documented response to recurrent or progressive disease is first met, assessed up to 5 years]
Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Duration of overall complete response [From documented CR to recurrent/ progressive disease, assessed up to 5 years]
Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Bone specific progression-free survival [Time to progression of bone specific disease over baseline, assessed up to 5 years]
Progression will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Duration of stable disease [Time from start of treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, assessed up to 5 years]
Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Incidence of adverse events (AE) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [Up to 5 years]
Toxicity will be graded. The highest AE grade per cycle will be reported in the electronic case report form (eCRF) from start of therapy until the end of treatment visit.

Other Outcome Measures

Rate of normalization of the total alkaline phosphatase level [Baseline up to 5 years]
The rate of normalization of the total alkaline phosphatase level (defined as a return to a value within the normal range) at the end of protocol therapy in patients with total alkaline phosphatase values above the upper limit of the normal range at baseline will be assessed.
Genomic mutations analysis [Up to 5 years]
Immune biomarker analysis [Up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Documented informed consent of participant and/or legally authorized representative
Agreement to provide archival primary or metastatic tumor tissue if available
Eastern Cooperative Oncology Group (ECOG) =< 2
Life expectancy > 12 months
Histologic diagnosis of prostate adenocarcinoma

Pure small cell carcinoma will be excluded; however, component of neuroendocrine /small cell differentiation will be allowed provided that adenocarcinoma constitutes majority of the tissue specimen

Stage M1

Metastatic disease can be documented by bone scan or computed tomography (CT) scan or magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT or the combination of these tests

Up to 4 metastatic lesions:
Must have at least 1 bone lesion AND each non-visceral lesion should be less than 5 cm
Visceral lesions will be limited to one lung lesion (< 2 cm) or one lymph node; no liver lesions allowed; lymph nodes allowed provided they are not in a field of prior radiation, and if amenable to SBRT (to be reviewed by principal investigator [PI])
Two lesions can be in close proximity (i.e. within 5 cm of each other) if they meet radiation SBRT normal tissue toxicity requirements
If have untreated primary prostate cancer: must undergo debulking prostatectomy
If had prior definitive radiation therapy to the prostate: no evidence of locally persistent or recurrent prostate cancer on digital rectal exam (DRE) and imaging studies (CT or MRI); retreatment to local residual-recurrent disease will result in potential eligibility to be reviewed by PI on a case-by-case basis
Does not have castration resistant disease

Castration resistance defined as progression of disease despite serum testosterone level of < 50 ng/dL

PSA >= 0.2 prior to start of androgen deprivation treatment
Initiated 28 (+ 7) days of androgen deprivation therapy (ADT) prior to day 1 of protocol therapy

Only luteinizing hormone-releasing hormone (LHRH) agonist/antagonist treatment is considered ADT, bicalutamide or other antiandrogens used alone do not count

May have received prior hormonal therapy in the context of definitive treatment of a primary tumor

Patients may have had one prior systemic non-chemotherapeutic treatment (i.e. immunotherapy, receptor tyrosine kinase inhibitor, antiangiogenic agent, differentiating agent) for recurrent or metastatic disease

Must have refused standard of care chemotherapy for metastatic disease
Recovered from all acute side-effects (except alopecia) related to previous systemic therapy
Absolute neutrophil count (ANC) >= 1,500/mm^3 (to be performed within 14 days prior to day 1 of protocol therapy)

NOTE: growth factor support is not permitted to normalize baseline ANC parameters, however subsequent growth factor administration is permitted as standard supportive care

Platelets >= 100,000/mm^3 (to be performed within 14 days prior to day 1 of protocol therapy)

NOTE: transfusion of blood products are not allowed to normalize baseline blood parameters, however subsequent transfusions are allowed per standard supportive care guidelines

Hemoglobin (HgB) >= 9.0 g/dL (to be performed within 14 days prior to day 1 of protocol therapy)

NOTE: transfusion of blood products are not allowed to normalize baseline blood parameters, however subsequent transfusions are allowed per standard supportive care guidelines

Total serum bilirubin =< 2 x upper limit of normal (ULN) (to be performed within 14 days prior to day 1 of protocol therapy)
Aspartate aminotransferase (AST) =< 2.5 x ULN (to be performed within 14 days prior to day 1 of protocol therapy)
Alanine aminotransferase (ALT) =< 2.5 x ULN (to be performed within 14 days prior to day 1 of protocol therapy)
Creatinine =< 2.5 mg/dL (to be performed within 14 days prior to day 1 of protocol therapy)

Exclusion Criteria:

Prior radium Ra 223 dichloride
Prior or concomitant chemotherapy for metastatic or recurrent disease with the following exceptions:
Prior chemotherapy for local primary disease is permitted
Bisphosphonates or receptor activator of nuclear factor kappa-Β (RANK) ligand inhibitors are allowed at doses and schedule consistent with the treatment or prevention of osteoporosis
Prior radiation treatment for metastatic disease
Concomitant radiation treatment to primary prostate site
Orchiectomy
Unstable medical comorbidities (i.e. uncontrolled cardiac comorbidities)
Metastases that in the judgment of investigator-radiologist are not amenable to SBRT
History of brain metastases or who currently have treated or untreated brain metastases
Uncontrolled human immunodeficiency virus (HIV) infection
Any other condition that would, in the investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)