Prostate Cancer
Conditions
Keywords
Prostate Cancer, Radiotherapy, SBRT, Stereotactic Body Radiotherapy, MRI
Brief summary
This study utilizes advanced imaging techniques (mpMRI prostate scan) to select and stratify patients for two different radiotherapy regimens based on the presence/absence of identifiable intraprostatic lesions. In patients without identifiable prostate cancer lesions, SBRT to the prostate in 5 sessions (fractions) will be administered. In patients with MRI-identified lesion(s), pelvic IMRT in 25 fractions will be administered followed by an SBRT prostate boost while simultaneously treating the prostate cancer lesion(s) to a higher dose in 3 fractions.
Detailed description
Radiotherapy (RT) is considered standard of care treatment for prostate cancer. Conventional RT regimens consist of 8-9 weeks of daily RT. Recent data support the use of hypofractionated RT (5-6 weeks) due to similar disease control in a contracted treatment time. This study combines the benefits of RT dose escalation while shortening the overall RT treatment course. In this protocol, patients will undergo a pretreatment mpMRI prostate scan and be stratified to two separate SBRT regimens depending on whether prostate lesions are present. For patients without any positive mpMRI lesions, an SBRT monotherapy (36.25 Gy in 5 fractions) approach will be utilized. Patients with an equivocal or positive mpMRI lesion(s), will receive IG-IMRT (45 Gy in 25 fractions) to prostate and seminal vesicle +/- lymph nodes followed by a SBRT whole prostate boost (18 Gy in 3 fractions) with a simultaneously integrated boost (SIB) (21 Gy in 3 fractions) to intraprostatic lesion(s) only. Patients will be regularly assessed every 3 months for the first 2 years and then every 6 months, indefinitely. Side effects will be monitored using the standardized international prostate symptom score (I-PSS) and Sexual Health Inventory of Men (SHIM) questionnaires at baseline and subsequent follow-up appointments. Hypothesis: MRI-guided treatment planning and delivery can selectively target high-risk prostate cancer nodules and deliver a higher effective RT dose, to achieve maximal tumor control without increasing toxicity, all in a shortened treatment duration.
Interventions
RADIATIONSBRT to whole prostate
Those patients with negative mpMRI prostate scan (PI-RADS 0-2) will receive SBRT (36.25 Gy/5 fractions) to the whole prostate
RADIATIONIMRT followed by mpMRI guided SBRT boost with SIB to intraprostatic lesions
Patients with positive or equivocal mpMRI prostate scan (PI-RADS 3-5) will receive IMRT (45 Gy/25 fractions) to the prostate + seminal vesicles +/- lymph nodes followed by SBRT boost (18 Gy/3 fractions) to the whole prostate with simultaneous integrated boost (21 Gy/3 fractions) to MRI defined intraprostatic lesions
Sponsors
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Biopsy proven prostate adenocarcinoma within 1 year of randomization * NCCN Low to High Risk localized prostate cancer * Zubrod Performance Status 0-1 within 60 days prior to registration
Exclusion criteria
* Prior or concurrent invasive malignancy (except non-melanoma skin cancer) * Regional Lymph Node (N1) involvement * Distant Metastases (M1) involvement * History of prior pelvic irradiation (external beam radiotherapy or brachytherapy) * Prior chemotherapy * Severe, active co-morbidities (unstable angina and/or CHF; MI; COPD; liver disease; AIDS) * Acute bacterial or fungal infection requiring IV antibiotics * Inability to undergo MRI * Inability to receive fiducial markers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Late Radiation Induced Genitourinary and Gastrointestinal Toxicity | 18 months | Number of Participants with late grade 3-5 genitourinary and gastrointestinal toxicity following mpMRI guided radiation treatment. Late toxicity will be defined as toxicity occurring more than nine months from the start of radiotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Acute Radiation Induced Genitourinary Adverse Event | 3 months | Adverse acute events are evaluated by the CTEP Active Version of the NCI CTCAE. The treatment-related attribution includes definitely, probably or possibly related to treatment. An acute adverse event is defined as the first occurrence of worst severity of the adverse event ≤30 days after the completion of RT. For each cohort, we will evaluate the acute radiation therapy-related adverse events. Specifically, we are interested in the percentage of acute GI and GU Grade 3+ adverse events that occur in each arm, which is considered to be similar to the high RT dose arm of RTOG 0126 in terms of RT dose. For this arm, a reported 1% of patients experienced Grade 3+ GI/GU acute toxicity, with no patient experiencing Grade 4 or 5 toxicities. If either hypofractionated arm has an acceptable percentage, then that arm will be deemed to have an acceptable adverse event profile. We will report the percentage for each arm as well as the one-sided 97.5% confidence interval. |
| Biochemical Recurrence | 18 months | Biochemical (PSA) recurrence is defined according to the proposed new Radiation Therapy Oncology Group/American Society for Therapeutic Radiology and Oncology (RTOG-ASTRO) criteria also known as the RTOG Phoenix definition: an increase of the PSA level at least 2 ng/mL greater than the minimum level reached after therapy (lowest PSA+ 2 criterion). PSA failure at 1, 2, and 5 years will be estimated for each cohort by the cumulative incidence method. |
| Disease Free-Survival | 18 months | The disease-free survival duration will be measured from the date of registration to the date of documentation of disease progression or until the date of death from any cause. DFS at 1, 2, and 5 years will be estimated for each c o h o r t by the Kaplan-Meier method. Also, 95% confidence intervals will be reported. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDian Wang, MD, PhD
Rush University Medical Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Negative mpMRI Prostate Scan SBRT to the whole prostate
SBRT to whole prostate: Those patients with negative mpMRI prostate scan (PI-RADS 0-2) will receive SBRT (36.25 Gy/5 fractions) to the whole prostate | 4 |
| Positive mpMRI Prostate Scan IMRT to the prostate + seminal vesicles followed by SBRT boost to the whole prostate with SIB to MRI defined intraprostatic lesions
IMRT followed by mpMRI guided SBRT boost with SIB to intraprostatic lesions: Patients with positive or equivocal mpMRI prostate scan (PI-RADS 3-5) will receive IMRT (45 Gy/25 fractions) to the prostate + seminal vesicles +/- lymph nodes followed by SBRT boost (18 Gy/3 fractions) to the whole prostate with simultaneous integrated boost (21 Gy/3 fractions) to MRI defined intraprostatic lesions | 50 |
| Total | 54 |
Baseline characteristics
| Characteristic | Positive mpMRI Prostate Scan | Total | Negative mpMRI Prostate Scan |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 34 Participants | 36 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 18 Participants | 2 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 50 participants | 54 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 50 Participants | 54 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 4 / 50 |
| other Total, other adverse events | 0 / 4 | 0 / 50 |
| serious Total, serious adverse events | 4 / 4 | 50 / 50 |
Outcome results
Primary
Number of Participants With Late Radiation Induced Genitourinary and Gastrointestinal Toxicity
Number of Participants with late grade 3-5 genitourinary and gastrointestinal toxicity following mpMRI guided radiation treatment. Late toxicity will be defined as toxicity occurring more than nine months from the start of radiotherapy.
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Negative mpMRI Prostate Scan | Number of Participants With Late Radiation Induced Genitourinary and Gastrointestinal Toxicity | 4 participants |
| Positive mpMRI Prostate Scan | Number of Participants With Late Radiation Induced Genitourinary and Gastrointestinal Toxicity | 50 participants |
Secondary
Biochemical Recurrence
Biochemical (PSA) recurrence is defined according to the proposed new Radiation Therapy Oncology Group/American Society for Therapeutic Radiology and Oncology (RTOG-ASTRO) criteria also known as the RTOG Phoenix definition: an increase of the PSA level at least 2 ng/mL greater than the minimum level reached after therapy (lowest PSA+ 2 criterion). PSA failure at 1, 2, and 5 years will be estimated for each cohort by the cumulative incidence method.
Time frame: 18 months
Secondary
Disease Free-Survival
The disease-free survival duration will be measured from the date of registration to the date of documentation of disease progression or until the date of death from any cause. DFS at 1, 2, and 5 years will be estimated for each c o h o r t by the Kaplan-Meier method. Also, 95% confidence intervals will be reported.
Time frame: 18 months
Secondary
Number of Participants With Acute Radiation Induced Genitourinary Adverse Event
Adverse acute events are evaluated by the CTEP Active Version of the NCI CTCAE. The treatment-related attribution includes definitely, probably or possibly related to treatment. An acute adverse event is defined as the first occurrence of worst severity of the adverse event ≤30 days after the completion of RT. For each cohort, we will evaluate the acute radiation therapy-related adverse events. Specifically, we are interested in the percentage of acute GI and GU Grade 3+ adverse events that occur in each arm, which is considered to be similar to the high RT dose arm of RTOG 0126 in terms of RT dose. For this arm, a reported 1% of patients experienced Grade 3+ GI/GU acute toxicity, with no patient experiencing Grade 4 or 5 toxicities. If either hypofractionated arm has an acceptable percentage, then that arm will be deemed to have an acceptable adverse event profile. We will report the percentage for each arm as well as the one-sided 97.5% confidence interval.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Negative mpMRI Prostate Scan | Number of Participants With Acute Radiation Induced Genitourinary Adverse Event | 4 participants |
| Positive mpMRI Prostate Scan | Number of Participants With Acute Radiation Induced Genitourinary Adverse Event | 50 participants |