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

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ClinicalTrials.gov Identifier: NCT03361735
Recruitment Status : Recruiting
First Posted : December 5, 2017
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center

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

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
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 : August 29, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Time to treatment failure [ Time Frame: 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.

  2. Objective response rate [ Time Frame: 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 :
  1. Progression-free survival [ Time Frame: 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.

  2. Overall survival [ Time Frame: From date of initiation of protocol treatment to date of death from any cause, assessed up to 5 years ]
  3. Complete response (CR) rate defined as the proportion of patients achieving CR [ Time Frame: Up to 5 years ]
    Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.

  4. Duration of response [ Time Frame: 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.

  5. Duration of overall complete response [ Time Frame: 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.

  6. Bone specific progression-free survival [ Time Frame: 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.

  7. Duration of stable disease [ Time Frame: 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.

  8. Incidence of adverse events (AE) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 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:
  1. Rate of normalization of the total alkaline phosphatase level [ Time Frame: 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.

  2. Genomic mutations analysis [ Time Frame: Up to 5 years ]
  3. Immune biomarker analysis [ Time Frame: Up to 5 years ]


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:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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): NCT03361735


Contacts
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Contact: Savita Dandapani, MD 626 256-4673 sdandapani@coh.org

Locations
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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Savita Dandapani, MD    626-256-4673      
Principal Investigator: Savita Dandapani, MD         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
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Principal Investigator: Savita Dandapani, MD City of Hope Medical Center

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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT03361735     History of Changes
Other Study ID Numbers: 17085
NCI-2017-02192 ( Registry Identifier: NCI CTRP )
First Posted: December 5, 2017    Key Record Dates
Last Update Posted: November 27, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by City of Hope Medical Center:
PSA Level Greater than or Equal to 0.2
Stage IV Prostate Adenocarcinoma AJCC v7

Additional relevant MeSH terms:
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Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Hormones
Leuprolide
Goserelin
Radium Ra 223 dichloride
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents