Clinical Trials /

High-Dose Brachytherapy in Treating Patients With Prostate Cancer

NCT02346253

Description:

This phase I/II trial studies the side effects and how well high-dose brachytherapy works in treating patients with prostate cancer that has not spread to other parts of the body. Brachytherapy is a type of radiation therapy in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near a tumor and may be a better treatment in patients with prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: High-Dose Brachytherapy in Treating Patients With Prostate Cancer
  • Official Title: A Phase I/II Study of High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: PROS0065
  • SECONDARY ID: NCI-2015-00089
  • SECONDARY ID: 40947
  • NCT ID: NCT02346253

Conditions

  • Prostate Adenocarcinoma
  • Stage I Prostate Cancer
  • Stage IIA Prostate Cancer
  • Stage IIB Prostate Cancer
  • Stage III Prostate Cancer

Interventions

DrugSynonymsArms
BicalutamideCDXTreatment (HDR brachytherapy, ADT and LHRH agonist therapy)
Leuprolide AcetateA-43818Treatment (HDR brachytherapy, ADT and LHRH agonist therapy)
Goserelin AcetateICI-118630, ZDX, ZoladexTreatment (HDR brachytherapy, ADT and LHRH agonist therapy)
Triptorelin PamoatePamorelin, TrelstarTreatment (HDR brachytherapy, ADT and LHRH agonist therapy)
DegarelixFE200486, FirmagonTreatment (HDR brachytherapy, ADT and LHRH agonist therapy)

Purpose

This phase I/II trial studies the side effects and how well high-dose brachytherapy works in treating patients with prostate cancer that has not spread to other parts of the body. Brachytherapy is a type of radiation therapy in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near a tumor and may be a better treatment in patients with prostate cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate the rate of acute (within six months of high-dose rate [HDR] completion) grade
      >= 2 genitourinary (GU) toxicity following high-dose-rate (HDR) brachytherapy (BT) as
      monotherapy for newly diagnosed prostate cancer using the National Cancer Institute's Common
      Terminology Criteria for Adverse Events, version 3 (CTCAE v3.0).

      SECONDARY OBJECTIVES:

      I. To estimate the proportion of men with a prostate-specific antigen (PSA) nadir by one year
      (nPSA12) of < 2 ng/mL.

      II. To estimate the rate of freedom from biochemical failure at 5 years (FFBF). III. To
      evaluate patient-reported quality of life via the 32-item Expanded Prostate Cancer Index
      Composite (EPIC).

      IV. To assess the cost-effectiveness of HDR BT as monotherapy for prostate cancer using the
      6-item European Quality of Life 5-Dimensions (EQ-5D).

      V. To explore pre-treatment clinical risk factors to optimize patient selection for HDR BT as
      monotherapy for prostate cancer.

      VI. To compare acute and late (> 6 months after HDR completion) GU and gastrointestinal (GI)
      grade >= 2 toxicity using CTCAE v3.0 and v4.0.

      VII. To explore dosimetric predictors of toxicity.

      OUTLINE:

      Patients undergo high-dose-rate brachytherapy over 2 fractions. Patients may receive androgen
      deprivation therapy (ADT) comprising bicalutamide orally (PO) once daily (QD). Patients may
      also receive luteinizing hormone-releasing hormone (LHRH) agonist therapy comprising
      leuprolide acetate intramuscularly (IM) or subcutaneously (SC), goserelin acetate SC,
      triptorelin pamoate IM, or degarelix SC for 4-6 months (intermediate-risk patients receiving
      ADT) or 6-36 months (high-risk patients) at the discretion of the treating physician.

      After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months, and
      then yearly for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (HDR brachytherapy, ADT and LHRH agonist therapy)ExperimentalPatients undergo high-dose-rate brachytherapy over 2 fractions. Patients also receive ADT comprising bicalutamide PO QD. Patients may also receive LHRH agonist therapy comprising leuprolide acetate IM or SC, goserelin acetate SC, triptorelin pamoate IM, or degarelix SC for 4-6 months (intermediate-risk patients receiving ADT) or 6-36 months (high-risk patients) at the discretion of the treating physician.
  • Bicalutamide
  • Leuprolide Acetate
  • Goserelin Acetate
  • Triptorelin Pamoate
  • Degarelix

Eligibility Criteria

        Inclusion Criteria:

          -  Documented pathologic confirmation of prostate adenocarcinoma

          -  Clinical T-classification T1-3

          -  PSA < 150 ng/mL

          -  Gleason score 6-10

          -  No evidence of distant metastasis based on a history/physical examination (to include
             at least digital rectal examination of the prostate and assessment of the abdomen and
             skeletal system)

          -  Clinically negative lymph nodes as established by abdomino-pelvic CT, no more than 90
             days prior toregistration; CT only for clinical classification of > T3- (with contrast
             if renal function is acceptable; a non-contrast CT is permitted if the patient is not
             a candidate for contrast) or magnetic resonance imaging (MRI), nodal sampling, or
             dissection. Patients with lymph nodes equivocal or questionable by imaging are
             eligible if the nodes are <1 cm in short axis.

          -  No evidence of bone metastases (M0) on bone scan (sodium fluoride [NaF] positron
             emission tomography [PET]/CT is an acceptable substitute) performed no more than 120
             days prior to registration; equivocal bone scan findings are allowed if plain films
             and/or MRI are negative for definite metastases

          -  American Urological Association Symptom Index (AUA SI) =< 15

          -  No prior transurethral resection of prostate (TURP)

        Exclusion Criteria:

          -  Clinical T4 disease

          -  N1 patients are ineligible, as are those with pelvic lymph nodes >= 1 cm in short axis
             diameter, defined as pathologically enlarged per Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1, by CT or MRI of the abdomen and pelvis, unless the enlarged lymph
             nodes are negative after sampling

          -  PSA >= 150 ng/mL

          -  AUA SI > 15

          -  History of radical prostatectomy, external beam radiotherapy (EBRT), or BT for
             prostate cancer

          -  Prior invasive malignancy (except non-melanoma skin cancer), unless disease-free for
             at least 3 years; no patient with a history of pelvic or hematologic malignancy is
             eligible, regardless of disease-free interval

          -  Previous chemotherapy for any malignancy, if given within three years of registration

          -  Past history of other investigational agents

          -  History of rectal surgery

          -  History of rectal fistula

          -  History of inflammatory bowel disease

          -  Severe, active co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last six months

               -  Transmural myocardial infarction within the last six months

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy at the time of registration

               -  Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C liver
                  disease

               -  Human immunodeficiency virus (HIV)-positivity with cluster of differentiation
                  (CD)4 count < 200 cells/microliter; note that HIV-positive patients are eligible,
                  provided they are under treatment with highly active antiretroviral therapy
                  (HAART) and have a CD4 count >= 200 cells/microliter no more than 30 days prior
                  to registration; note also that HIV testing is not required for eligibility on
                  this protocol

          -  End-stage renal disease (i.e., any patient requiring or advised to undergo dialysis)

          -  Prior allergic reaction to the study drug(s) involved in this protocol
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients with acute grade 2 or greater acute GU toxicity, scored according to CTCAE v3.0
Time Frame:Within 6 months of HDR completion
Safety Issue:
Description:Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.

Secondary Outcome Measures

Measure:Proportion of men with a nPSA12 of < 2 ng/mL
Time Frame:Up to 1 year after completion of HDR
Safety Issue:
Description:nPSA12 is defined as the lowest PSA level achieved during the first year after completing HDR.
Measure:FFBF (Biochemical failure define according to PSA nadir+2ng/mL and 3 consecutive rises definition according to American Society of Radiation Oncology
Time Frame:From the completion of all treatment to the time of BF, assessed at 5 years
Safety Issue:
Description:Biochemical failure (BF) will be defined according the PSA nadir + 2 ng/mL and three consecutive rises definition according to the American Society of Radiation Oncology consensus recommendation. Time to first BF will be analyzed with competing risk models with death as a competing risk.
Measure:Change in quality of life as measured by EPIC scores
Time Frame:Baseline to up to 5 years
Safety Issue:
Description:
Measure:Cost-effectiveness of HDR BT as monotherapy for prostate cancer using as measured by EQ-5D scores
Time Frame:Up to 5 years
Safety Issue:
Description:Measured utility values for each patient on this study will be combined with overall survival to calculate the "QALY" quality-adjusted life years.
Measure:Pre-treatment clinical risk factors to optimize patient selection for HDR BT as monotherapy for prostate cancer (association between each risk factor and the risk of having a first BF)
Time Frame:Baseline
Safety Issue:
Description:Clinical risk factors will be tested in competing risk models to evaluate the association between each risk factor and the risk of having a first BF.
Measure:Proportion of patients with acute grade 2 or greater acute GU toxicity, scored according to CTCAE v4.0
Time Frame:Within 6 months of HDR completion
Safety Issue:
Description:Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.
Measure:Late GU toxicity, scored according to CTCAE v3.0 and v4.0
Time Frame:Up to 5 years
Safety Issue:
Description:Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.
Measure:Acute GI toxicity scored according to CTCAE v3.0 and CTCAE v4.0
Time Frame:Up to 6 months after completing HDR BT
Safety Issue:
Description:Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.
Measure:Late GI toxicity, scored according to CTCAE v3.0 and CTCAE v4.0
Time Frame:Up to 5 years
Safety Issue:
Description:Will be calculated with a 90% confidence interval. Treatment plans will be reviewed, and doses to normal structures will be calculated and tabulated to determine possible relationships with toxicity outcomes.
Measure:Dosimetric predictors of toxicity (Doses to pelvic structures will be calculated and reviewed to determine possible correlations with toxicity outcomes)
Time Frame:Up to 5 years
Safety Issue:
Description:Doses to pelvic structures will be calculated and reviewed to determine possible correlations with toxicity outcomes.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Stanford University

Last Updated

August 14, 2019