Clinical Trials /

Hypofractionated Accelerated Pelvic Nodal Radiotherapy (GCC 2048)

NCT04486755

Description:

A phase I trial to determine the safety of delivering three sequentially shorter RT schedules (20, 16, and 12 fractions) of HypoFx pelvic nodal RT in combination with a HypoFx, simultaneous integrated boost (SIB) to the prostate that have been designed to incrementally increased the biological equivalent dose (BED) to prostate cancer, while maintaining a constant BED to normal tissue toxicity.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Hypofractionated Accelerated Pelvic Nodal Radiotherapy (GCC 2048)
  • Official Title: A Phase I Dose Escalation Study of Hypofractionated Accelerated Pelvic Nodal Radiotherapy Delivered With A Simultaneously Integrated Prostate Boost For Patients With Localized, Intermediate- And High-Risk Prostate Cancer (GCC 2048)

Clinical Trial IDs

  • ORG STUDY ID: HP-00091499
  • NCT ID: NCT04486755

Conditions

  • Prostate Cancer
  • Prostate Adenocarcinoma

Purpose

A phase I trial to determine the safety of delivering three sequentially shorter RT schedules (20, 16, and 12 fractions) of HypoFx pelvic nodal RT in combination with a HypoFx, simultaneous integrated boost (SIB) to the prostate that have been designed to incrementally increased the biological equivalent dose (BED) to prostate cancer, while maintaining a constant BED to normal tissue toxicity.

Detailed Description

      Outcomes for patients with unfavorable intermediate-risk and high-risk prostate cancer (PC)
      have been historically poor and are now known to require multimodality treatment. A standard
      non-surgical treatment option for patients with localized, intermediate and high-risk PC is
      radiation therapy (RT) in combination with short- or long-term androgen deprivation therapy
      (ADT).

      The benefit of pelvic nodal RT in this setting is unclear, previous studies have been
      equivocal. There is a growing body of evidence to demonstrate that use of hypofractionated
      (HypoFx) RT may be a safe method for increasing the dose of RT, while also decreasing normal
      tissue toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Level 1ExperimentalDose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 20 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.
    Dose Level 2ExperimentalDose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 16 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.
      Dose Level 3ExperimentalDose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 12 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.

        Eligibility Criteria

                Inclusion Criteria:
        
                  1. Patient age is ≥ 18 years
        
                  2. Pathologically (histologically or cytologically) proven diagnosis of prostatic
                     adenocarcinoma within 180 days of registration.
        
                  3. Patient's with intermediate to high risk prostate cancer and must be recommended to
                     undergo pelvic as well as prostatic irradiation.
        
                  4. History/physical examination (to include at a minimum digital rectal examination of
                     the prostate and examination of the skeletal system and abdomen) within 90 days prior
                     to registration.
        
                  5. Clinically negative lymph nodes as established by imaging (pelvic ± abdominal CT or
                     MR), (but not by nodal sampling, or dissection) within 120 days prior to registration.
        
                     • Patients with lymph nodes equivocal or questionable by imaging are eligible if the
                     nodes are ≤ 1.5 cm.
        
                  6. No evidence of bone metastases (M0) on bone scan within 120 days prior to
                     registration.
        
                     • Equivocal bone scan findings are allowed if plain films (or CT or MRI) are negative
                     for metastasis.
        
                  7. Baseline serum PSA value performed within 12 weeks (90 days) prior to registration.
        
                  8. ECOG Performance Status 0-1
        
                  9. Patient must be able to provide study specific informed consent prior to study entry.
        
                Exclusion Criteria:
        
                  1. Evidence of distant metastases
        
                  2. Regional lymph node involvement
        
                  3. Previous radical surgery (prostatectomy), cryosurgery, or HIFU (High-intensity focused
                     ultrasound) for prostate cancer
        
                  4. Previous pelvic irradiation or prostate brachytherapy
        
                  5. Planned prostate brachytherapy boost
        
                  6. Previous or concurrent cytotoxic chemotherapy for prostate cancer
        
                  7. Severe acute or chronic medical or psychiatric condition or laboratory abnormality
                     that may increase the risk associated with study participation or study drug
                     administration, or may interfere with the interpretation of study results, and in the
                     judgment of the investigator would make the subject inappropriate for entry into this
                     study.
        
                  8. Patients are excluded if they have a history of autoimmune disease that, in the
                     opinion of the treating physician would be a contraindication to pelvic radiation
                     (e.g., active systemic lupus, progressive scleroderma)
        
                  9. Patients receiving full-dose anticoagulation or clopidogrel
        
                     • Patients taking 81 mg Aspirin po daily may are still eligible for the study
        
                 10. Patients with a history of prior small bowel ulceration
              
        Maximum Eligible Age:N/A
        Minimum Eligible Age:18 Years
        Eligible Gender:Male
        Healthy Volunteers:No

        Primary Outcome Measures

        Measure:HypoFx RT schedule that results in <33% acute dose-limiting toxicity with accelerated, HypoFx pelvic nodal RT
        Time Frame:Within 90 days of completing RT
        Safety Issue:
        Description:The frequency of all observed acute GI, GU, hematologic, and neurologic dose limiting toxicities by CTCAE v5 grade will be tabulated. DLT is defined as treatment-related: Grade ≥3 GI (small bowel or rectal) toxicity, Grade ≥3 GU toxicity, Grade ≥3 hematologic, Grade ≥3 neurologic toxicity, or any grade 5 treatment-related adverse events.

        Secondary Outcome Measures

        Measure:Frequency of acute and late GI, GU, hematologic, and neurologic toxicity for each dose cohort
        Time Frame:Acute (within 90 days completing RT), Late (occurring > 90 days from treatment), 3-months, 6 months, 1-year and 2 years
        Safety Issue:
        Description:The frequency of the maximum grade acute (within 90 days completing RT) and late (occurring > 90 days from treatment) GI (small bowel and rectal), GU, hematologic, and neurologic toxicities at 3-months, 6 months, 1-year and 2 years for each dose cohort using National Cancer Institute Common Terminology Criteria v.5.0 (NCI CTCAE v5).
        Measure:Dose volume histogram (DVH) parameters
        Time Frame:Within 90 days of completing RT
        Safety Issue:
        Description:A dose-volume histogram is a histogram relating radiation dose to tissue volume in radiation therapy planning.
        Measure:Evaluate the duration of biochemical progression-free survival
        Time Frame:2 years after completing RT
        Safety Issue:
        Description:The duration of bPFS will be measured from the end of RT until either PSA recurrence or death due to any cause and summarized for the expanded cohort of patients treated at the maximum total dose (MTD). PSA recurrence is defined by the Phoenix definition of biochemical failure (PSA nadir + 2 ng/mL).
        Measure:Patient Reported Outcomes (PROs) related to urinary and bowel function
        Time Frame:1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2
        Safety Issue:
        Description:Quality of life will be assessed with the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire.
        Measure:Patient Reported Outcomes (PROs) related to urinary function
        Time Frame:1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2
        Safety Issue:
        Description:The International Prostate System Score (IPSS) questionnaire will be used for urinary function.
        Measure:Patient Reported Outcomes (PROs) related to urinary and bowel function
        Time Frame:1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2
        Safety Issue:
        Description:The PRO-CTCAE questionnaire measures patient-reported bowel, urinary and sexual function.

        Details

        Phase:Phase 1
        Primary Purpose:Interventional
        Overall Status:Not yet recruiting
        Lead Sponsor:University of Maryland, Baltimore

        Trial Keywords

        • Prostate
        • Hypofractionated Radiation Therapy
        • Prostate Cancer
        • Radiotherapy
        • Proton Therapy

        Last Updated

        July 21, 2020