Clinical Trials /

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

NCT03361735

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 17085
  • SECONDARY ID: NCI-2017-02192
  • NCT ID: NCT03361735

Conditions

  • Prostate Adenocarcinoma

Interventions

DrugSynonymsArms
Leuprolide Acetate377526, 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, ViadurTreatment (hormone therapy, SBRT, radium Ra 223 dichloride)
Goserelin Acetate606864, 65807-02-5, D-Ser(bu(t))(6)azgly(10)-LHRH Acetate, ZDX, ZoladexTreatment (hormone therapy, SBRT, radium Ra 223 dichloride)
Degarelix214766-78-6, FE200486, FirmagonTreatment (hormone therapy, SBRT, radium Ra 223 dichloride)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      I. To assess the safety of adding radium Ra 223 dichloride to SBRT and ADT in patients with
      oligometastatic castration sensitive prostate cancer.

      II. To assess the prostate-specific antigen (PSA) and overall response rate (ORR) after 6
      cycles of radium Ra 223 dichloride (cycle 8 day 1).

      III. 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.

      IV. 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.

      V. 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.

      VI. 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:

      I. To perform exploratory analysis of primary or metastatic tumor mutation patterns in this
      study population at baseline.

      II. To identify immune system factors in the blood that change during the course of
      ADT-radiotherapy for metastatic prostate cancer.

      III. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (hormone therapy, SBRT, radium Ra 223 dichloride)ExperimentalBeginning 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.
  • Leuprolide Acetate
  • Goserelin Acetate
  • Degarelix

Eligibility 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time to treatment failure
Time Frame:Assessed up to 5 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Progression will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Measure:Overall survival
Time Frame:From date of initiation of protocol treatment to date of death from any cause, assessed up to 5 years
Safety Issue:
Description:
Measure:Complete response (CR) rate defined as the proportion of patients achieving CR
Time Frame:Up to 5 years
Safety Issue:
Description:Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Measure:Duration of response
Time Frame:From documented response to recurrent or progressive disease is first met, assessed up to 5 years
Safety Issue:
Description:Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Measure:Duration of overall complete response
Time Frame:From documented CR to recurrent/ progressive disease, assessed up to 5 years
Safety Issue:
Description:Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Measure:Bone specific progression-free survival
Time Frame:Time to progression of bone specific disease over baseline, assessed up to 5 years
Safety Issue:
Description:Progression will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Measure: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
Safety Issue:
Description:Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria.
Measure: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
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:City of Hope Medical Center

Trial Keywords

  • PSA Level Greater than or Equal to 0.2
  • Stage IV Prostate Adenocarcinoma AJCC v7

Last Updated

November 25, 2019