Brief Summary
The present study evaluates clinical outcomes and treatment-related toxicity following definitive ultra-high dose external beam radiotherapy delivered with two different regimens in patients with intermediate-risk adenocarcinoma of the prostate. Modern computer-driven technology enables the implementation of ultra-high hypofractionated Image-Guided Radiotherapy (IGRT) safely.
Prostate cancer patients classified according to the current National Comprehensive Cancer Network (NCCN) guidelines as intermediate risk (biopsy Gleason score of 7 and/or Prostate Specific Antigen (PSA) level \>10 and ≤20 ng/mL and/or Stage T1, T2a, T2b or T2c) are eligible for this study.
Patients will undergo IGRT with volumetric intensity-modulated arc radiotherapy (VMAT) with state-of-the-art treatment-planning and quality assurance procedures. Emphasis is placed on normal tissue sparing and delivery accuracy via the use of devices that ensure stability and beam location reproducibility. A rectal balloon with air filling will be used for prostate target immobilization and anatomical reproducibility, while a urethral catheter loaded with beacon transponders will be used to ensure set-up reproducibility and online target tracking. Previously untreated patients with intermediate-risk prostate cancer will be prospectively randomized to receive either 45 Gy in five fractions of 9 Gy each vs. 24 Gy in a single-dose.
Patients will be followed at one month post-treatment and every 3 months for up to 12 months (+/- 4 weeks) and every 6 months thereafter. Acute and chronic toxicity evaluations will focus on urinary, rectal and sexual functions and will be assessed through validated questionnaires. Serum PSA values will be regularly acquired during follow-up. A multiparametric MRI will be performed at baseline, 6, 12 and 24 months following intervention. Additionally, a post-treatment diffusion-weighted MRI (DW-MRI) will be performed within 15 minutes of the first treatment, to measure early physiologic changes, such as perfusion and ischemia, that may correlate with clinically relevant end-points. Post-treatment prostate needle biopsies will be obtained at 24 months to evaluate pathologic response to therapy. The study will be continuously monitored for a minimum of 5 years. In the event unexpected severe (grade ≥3) toxicities are observed in any one of the treatment arms, the study will be terminated according to the stopping rule \>3/first 15 patients.
Prostate cancer patients classified according to the current National Comprehensive Cancer Network (NCCN) guidelines as intermediate risk (biopsy Gleason score of 7 and/or Prostate Specific Antigen (PSA) level \>10 and ≤20 ng/mL and/or Stage T1, T2a, T2b or T2c) are eligible for this study.
Patients will undergo IGRT with volumetric intensity-modulated arc radiotherapy (VMAT) with state-of-the-art treatment-planning and quality assurance procedures. Emphasis is placed on normal tissue sparing and delivery accuracy via the use of devices that ensure stability and beam location reproducibility. A rectal balloon with air filling will be used for prostate target immobilization and anatomical reproducibility, while a urethral catheter loaded with beacon transponders will be used to ensure set-up reproducibility and online target tracking. Previously untreated patients with intermediate-risk prostate cancer will be prospectively randomized to receive either 45 Gy in five fractions of 9 Gy each vs. 24 Gy in a single-dose.
Patients will be followed at one month post-treatment and every 3 months for up to 12 months (+/- 4 weeks) and every 6 months thereafter. Acute and chronic toxicity evaluations will focus on urinary, rectal and sexual functions and will be assessed through validated questionnaires. Serum PSA values will be regularly acquired during follow-up. A multiparametric MRI will be performed at baseline, 6, 12 and 24 months following intervention. Additionally, a post-treatment diffusion-weighted MRI (DW-MRI) will be performed within 15 minutes of the first treatment, to measure early physiologic changes, such as perfusion and ischemia, that may correlate with clinically relevant end-points. Post-treatment prostate needle biopsies will be obtained at 24 months to evaluate pathologic response to therapy. The study will be continuously monitored for a minimum of 5 years. In the event unexpected severe (grade ≥3) toxicities are observed in any one of the treatment arms, the study will be terminated according to the stopping rule \>3/first 15 patients.
Brief Title
A Pilot Study of Ultra-High-Dose Hypofractionated or Single-Dose Radiotherapy for Intermediate Risk Prostate Cancer
Detailed Description
This is open label feasibility study where patients enrolled in the study will undergo image-guided, intensity-modulated radiotherapy using the same equipment, techniques, and treatment-planning procedures as currently practiced at CCU. Eligible patients will receive either 45 Gy in 5 sessions each of 9 Gy delivered in one week (arm A) or 24 Gy in 1 session (arm B) to assess the dose limiting toxicities in the two groups. Patients will be randomized to arm A or arm B.
Dose limiting toxicity (DLT) is defined as any Grade 3 urinary or rectal toxicity, based on NCI CTCAE v4.0, observed within 3 months of completion of protocol radiation. If, at any point in the conduct of the trial, DLTs are observed in three patients in a study arm, accrual to that arm will be terminated.
There are three aspects of this study that will be different from the currently used standard treatment for definitive external beam treatment of prostate cancer:
1. The dose-fractionation scheme, as per the treatment arm.
2. Acquisition of a set of prostate biopsies at 24 months post treatment
3. Examination of imaging response based on multi-parametric MRI
Dose limiting toxicity (DLT) is defined as any Grade 3 urinary or rectal toxicity, based on NCI CTCAE v4.0, observed within 3 months of completion of protocol radiation. If, at any point in the conduct of the trial, DLTs are observed in three patients in a study arm, accrual to that arm will be terminated.
There are three aspects of this study that will be different from the currently used standard treatment for definitive external beam treatment of prostate cancer:
1. The dose-fractionation scheme, as per the treatment arm.
2. Acquisition of a set of prostate biopsies at 24 months post treatment
3. Examination of imaging response based on multi-parametric MRI
Completion Date
Completion Date Type
Estimated
Conditions
Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
* Signed study specific informed consent form;
* Histologic confirmation of adenocarcinoma of the prostate by biopsy;
* PSA ≤ 20 ng/mL;
* Gleason score 7;
* Staging MRI must confirm American Joint Committee on Cancer (AJCC) stage T1, T2a, T2b or T2c;
* No direct evidence of regional or distant metastases after appropriate staging studies;
* Age ≥ 50;
* Performance Status 0-2;
* Internation Prostate Symptom Score score must be ≤ 15 (alpha blockers allowed);
* CT scan or Ultrasound-based volume estimation of prostate gland ≤ 100 grams;
Exclusion Criteria:
* Positive lymph-nodes or metastatic disease from prostate cancer on imaging studies
* Prior invasive malignancy unless disease-free for a minimum of 5 years
* Tumour Clinical stage T3 or T4 on MRI
* PSA \> 20 ng/mL
* Gleason score \> 7
* Previous pelvic radiotherapy
* Previous surgery for prostate cancer
* Previous transurethral resection of the prostate (TURP)
* History of Crohn's Disease or Ulcerative Colitis
* Previous significant urinary obstructive symptoms
* Significant psychiatric illness
* Ultrasound or CT estimate of prostate volume \> 100 grams
* Severe, active co-morbidity
* Signed study specific informed consent form;
* Histologic confirmation of adenocarcinoma of the prostate by biopsy;
* PSA ≤ 20 ng/mL;
* Gleason score 7;
* Staging MRI must confirm American Joint Committee on Cancer (AJCC) stage T1, T2a, T2b or T2c;
* No direct evidence of regional or distant metastases after appropriate staging studies;
* Age ≥ 50;
* Performance Status 0-2;
* Internation Prostate Symptom Score score must be ≤ 15 (alpha blockers allowed);
* CT scan or Ultrasound-based volume estimation of prostate gland ≤ 100 grams;
Exclusion Criteria:
* Positive lymph-nodes or metastatic disease from prostate cancer on imaging studies
* Prior invasive malignancy unless disease-free for a minimum of 5 years
* Tumour Clinical stage T3 or T4 on MRI
* PSA \> 20 ng/mL
* Gleason score \> 7
* Previous pelvic radiotherapy
* Previous surgery for prostate cancer
* Previous transurethral resection of the prostate (TURP)
* History of Crohn's Disease or Ulcerative Colitis
* Previous significant urinary obstructive symptoms
* Significant psychiatric illness
* Ultrasound or CT estimate of prostate volume \> 100 grams
* Severe, active co-morbidity
Inclusion Criteria
Inclusion Criteria:
* Signed study specific informed consent form;
* Histologic confirmation of adenocarcinoma of the prostate by biopsy;
* PSA ≤ 20 ng/mL;
* Gleason score 7;
* Staging MRI must confirm American Joint Committee on Cancer (AJCC) stage T1, T2a, T2b or T2c;
* No direct evidence of regional or distant metastases after appropriate staging studies;
* Age ≥ 50;
* Performance Status 0-2;
* Internation Prostate Symptom Score score must be ≤ 15 (alpha blockers allowed);
* CT scan or Ultrasound-based volume estimation of prostate gland ≤ 100 grams;
* Signed study specific informed consent form;
* Histologic confirmation of adenocarcinoma of the prostate by biopsy;
* PSA ≤ 20 ng/mL;
* Gleason score 7;
* Staging MRI must confirm American Joint Committee on Cancer (AJCC) stage T1, T2a, T2b or T2c;
* No direct evidence of regional or distant metastases after appropriate staging studies;
* Age ≥ 50;
* Performance Status 0-2;
* Internation Prostate Symptom Score score must be ≤ 15 (alpha blockers allowed);
* CT scan or Ultrasound-based volume estimation of prostate gland ≤ 100 grams;
Gender
Male
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
50 Years
NCT Id
NCT04147806
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2016-6545
Overall Status
Active, not recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Pilot Study of Ultra-High-Dose Hypofractionated or Single-Dose Radiotherapy for Intermediate Risk Prostate Cancer
Primary Outcomes
Outcome Description
The number of patients with treatment-related DLT will be based on the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 criteria. DLT is defined as any Grade 3 genitourinary or gastrointestinal toxicity based on NCI-CTCAE criteria observed within 3 months of completion of protocol radiation therapy. The number of patients exhibiting DLT will be summarized by study arm.
Outcome Measure
Dose-limiting toxicity (DLT)
Outcome Time Frame
1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment
Secondary Outcomes
Outcome Description
Serum blood draws will be collected for determination of PSA concentrations at the specified timepoints during clinical follow-up and analyzed by immunoassay. Change in serum PSA concentrations from baseline will be summarized in units of ng/mL and reported by study arm using basic descriptive statistics.
Outcome Time Frame
1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment
Outcome Measure
Change in Post-treatment Serum Prostate Specific Antigen (PSA) concentrations
Outcome Description
Post-treatment PSA-RFS will be assessed at the specified timepoints during clinical follow-up. PSA-RFS will be defined as the time from the end of radiation therapy to PSA relapse or last follow-up and based on the revised American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Houston definition. The key criterion for biochemical failure as defined by the updated ASTRO definition is a PSA level at or greater than the absolute nadir PSA level plus 2 ng/mL dated at the time of failure. PSA-RFS will be assessed by Kaplan-Meier estimation and summarized by arm at each timepoint.
Outcome Time Frame
1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment
Outcome Measure
Post-treatment Prostate Specific Antigen Relapse-free Survival (PSA-RFS)
Outcome Description
Pathological response rate will be evaluated via repeat biopsy samples. For purposes of this study, pathological response rate will be summarized using sample proportions (percentages) and confidence intervals. Pathologic response rates will be divided into 3 categories as per current institutional standard and summarized based on these categories:
1. Prostate adenocarcinoma without typical radiation induced changes;
2. Prostate adenocarcinoma with radiation induced changes; and
3. No evidence of adenocarcinoma.
1. Prostate adenocarcinoma without typical radiation induced changes;
2. Prostate adenocarcinoma with radiation induced changes; and
3. No evidence of adenocarcinoma.
Outcome Time Frame
24-36 months following completion of treatment
Outcome Measure
Pathological Response Rate
Outcome Description
The IPSS index will be utilized to measure the severity of lower urinary tract symptoms. The IPSS is a 7-item questionnaire designed to assess urinary functioning; specifically, urinary frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying, and urgency. Each of the 7 symptom questions is rated on a 6-point Likert scale ranging from 0-5, for an overall possible scoring range of 0-35, with higher scores indicating more difficulty in urinary functioning. Severity thresholds are as follows: 0-7 indicates mild symptoms; 8-19 indicates moderate symptoms; 20-35 indicates severe symptoms. Results will be summarized by arm for each timepoint using basic descriptive statistics.
Outcome Time Frame
1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment
Outcome Measure
Quality of life assessment based on International Prostate Symptom Score (IPSS)
Outcome Description
Qualify of life will also be assessed using the IIEF questionnaire. The IIEF is a 15-item questionnaire that assesses five distinct factors (i.e., erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall sexual satisfaction). Each of the 15 questions is rated on 6-point Likert scale ranging from 0-5, for an overall possible scoring range of 0-75. Higher scores are indicative of increased erectile function. Results will be summarized by arm for each timepoint using basic descriptive statistics.
Outcome Time Frame
1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months following completion of treatment
Outcome Measure
Quality of life assessment based on International Index of Erectile Function (IIEF)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
50
Investigators
Investigator Type
Principal Investigator
Investigator Name
Madhur Garg
Investigator Email
mgarg@montefiore.org
Investigator Phone
Categories Mesh Debug
Prostate Cancer --- PROSTATIC NEOPLASMS
Genitourinary (GU) & Urologic Cancers --- GENITAL NEOPLASMS, MALE
Genitourinary (GU) & Urologic Cancers --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
MeSH Terms
PROSTATIC NEOPLASMS
GENITAL NEOPLASMS, MALE
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
GENITAL DISEASES, MALE
GENITAL DISEASES
UROGENITAL DISEASES
PROSTATIC DISEASES
MALE UROGENITAL DISEASES
DEXAMETHASONE
TAMSULOSIN
PREGNADIENETRIOLS
PREGNADIENES
PREGNANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
STEROIDS, FLUORINATED
BENZENESULFONAMIDES
SULFONAMIDES
AMIDES
ORGANIC CHEMICALS
BENZENE DERIVATIVES
HYDROCARBONS, AROMATIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
SULFONES
SULFUR COMPOUNDS