Back to resultsHypofractionated Accelerated Pelvic Nodal Radiotherapy (GCC 2048)
Primary Purpose
Prostate Cancer, Prostate Adenocarcinoma
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hypofractionated Radiation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate, Hypofractionated Radiation Therapy, Prostate Cancer, Radiotherapy, Proton Therapy
Eligibility Criteria
Inclusion Criteria:
- Patient age is ≥ 18 years
- Pathologically (histologically or cytologically) proven diagnosis of prostatic adenocarcinoma within 180 days of registration.
- Patient's with intermediate to high risk prostate cancer and must be recommended to undergo pelvic as well as prostatic irradiation.
- 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.
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.
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.
- Baseline serum PSA value performed within 12 weeks (90 days) prior to registration.
- ECOG Performance Status 0-1
- Patient must be able to provide study specific informed consent prior to study entry.
Exclusion Criteria:
- Evidence of distant metastases
- Regional lymph node involvement
- Previous radical surgery (prostatectomy), cryosurgery, or HIFU (High-intensity focused ultrasound) for prostate cancer
- Previous pelvic irradiation or prostate brachytherapy
- Planned prostate brachytherapy boost
- Previous or concurrent cytotoxic chemotherapy for prostate cancer
- 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.
- 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)
Patients receiving full-dose anticoagulation or clopidogrel
• Patients taking 81 mg Aspirin po daily may are still eligible for the study
- Patients with a history of prior small bowel ulceration
Sites / Locations
- Maryland Proton Treatment CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Dose Level 1
Dose Level 2
Dose Level 3
Arm Description
Dose 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 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 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.
Outcomes
Primary Outcome Measures
HypoFx RT schedule that results in <33% acute dose-limiting toxicity with accelerated, HypoFx pelvic nodal RT
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
Frequency of acute and late GI, GU, hematologic, and neurologic toxicity for each dose cohort
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).
Dose volume histogram (DVH) parameters
A dose-volume histogram is a histogram relating radiation dose to tissue volume in radiation therapy planning.
Evaluate the duration of biochemical progression-free survival
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).
Patient Reported Outcomes (PROs) related to urinary and bowel function
Quality of life will be assessed with the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire.
Patient Reported Outcomes (PROs) related to urinary function
The International Prostate System Score (IPSS) questionnaire will be used for urinary function.
Patient Reported Outcomes (PROs) related to urinary and bowel function
The PRO-CTCAE questionnaire measures patient-reported bowel, urinary and sexual function.
Full Information
NCT ID
NCT04486755
First Posted
July 15, 2020
Last Updated
May 2, 2023
Sponsor
University of Maryland, Baltimore
1. Study Identification
Unique Protocol Identification Number
NCT04486755
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 19, 2020 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Prostate Adenocarcinoma
Keywords
Prostate, Hypofractionated Radiation Therapy, Prostate Cancer, Radiotherapy, Proton Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
A modified 3+3 study design will be employed to determine the dose-fractionation schedule that results in less than 33% dose limiting toxicity. One de-escalation will be allowed if the initial dose-fractionation schedule results in too high a frequency of dose limiting toxicities. A total of 6 patients will be treated following the dose-fractionation schedule that is recommended for further study.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose Level 1
Arm Type
Experimental
Arm Description
Dose 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.
Arm Title
Dose Level 2
Arm Type
Experimental
Arm Description
Dose 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.
Arm Title
Dose Level 3
Arm Type
Experimental
Arm Description
Dose 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.
Intervention Type
Radiation
Intervention Name(s)
Hypofractionated Radiation Therapy
Intervention Description
All patients RT will be delivered utilizing pencil beam scanning proton therapy. Radiation treatment will be delivered 4 days per week.
Primary Outcome Measure Information:
Title
HypoFx RT schedule that results in <33% acute dose-limiting toxicity with accelerated, HypoFx pelvic nodal RT
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.
Time Frame
Within 90 days of completing RT
Secondary Outcome Measure Information:
Title
Frequency of acute and late GI, GU, hematologic, and neurologic toxicity for each dose cohort
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).
Time Frame
Acute (within 90 days completing RT), Late (occurring > 90 days from treatment), 3-months, 6 months, 1-year and 2 years
Title
Dose volume histogram (DVH) parameters
Description
A dose-volume histogram is a histogram relating radiation dose to tissue volume in radiation therapy planning.
Time Frame
Within 90 days of completing RT
Title
Evaluate the duration of biochemical progression-free survival
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).
Time Frame
2 years after completing RT
Title
Patient Reported Outcomes (PROs) related to urinary and bowel function
Description
Quality of life will be assessed with the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire.
Time Frame
1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2
Title
Patient Reported Outcomes (PROs) related to urinary function
Description
The International Prostate System Score (IPSS) questionnaire will be used for urinary function.
Time Frame
1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2
Title
Patient Reported Outcomes (PROs) related to urinary and bowel function
Description
The PRO-CTCAE questionnaire measures patient-reported bowel, urinary and sexual function.
Time Frame
1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient age is ≥ 18 years
Pathologically (histologically or cytologically) proven diagnosis of prostatic adenocarcinoma within 180 days of registration.
Patient's with intermediate to high risk prostate cancer and must be recommended to undergo pelvic as well as prostatic irradiation.
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.
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.
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.
Baseline serum PSA value performed within 12 weeks (90 days) prior to registration.
ECOG Performance Status 0-1
Patient must be able to provide study specific informed consent prior to study entry.
Exclusion Criteria:
Evidence of distant metastases
Regional lymph node involvement
Previous radical surgery (prostatectomy), cryosurgery, or HIFU (High-intensity focused ultrasound) for prostate cancer
Previous pelvic irradiation or prostate brachytherapy
Planned prostate brachytherapy boost
Previous or concurrent cytotoxic chemotherapy for prostate cancer
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.
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)
Patients receiving full-dose anticoagulation or clopidogrel
• Patients taking 81 mg Aspirin po daily may are still eligible for the study
Patients with a history of prior small bowel ulceration
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mark Mishra, MD
Phone
4103286080
Email
mmishra@umm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Acara Carter
Phone
410-369-5350
Email
acara.carter@umm.edu
Facility Information:
Facility Name
Maryland Proton Treatment Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Mishra, MD
Phone
410-328-6080
Email
mmishra@umm.edu
First Name & Middle Initial & Last Name & Degree
Acara Carter
Phone
410-369-5350
Email
acara.carter@umm.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Hypofractionated Accelerated Pelvic Nodal Radiotherapy (GCC 2048)
We'll reach out to this number within 24 hrs