Clinical trial NCT03624660: Dose-Escalated Proton Radiation Therapy for High-Risk Prostate Cancer
Official title: A Phase II Study of Dose-Escalated Proton-Based Radiation Therapy Delivered With a Simultaneous Integrated Boost (SIB) to Intraprostatic Tumors (IPT) Visible on Pretreatment Magnetic Resonance Image
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Adenocarcinoma of the Prostate
Keywords: High-risk
Prostate cancer
Proton Radiation
Dose-escalated
Hypofractionation
Simultaneous Integrated Boost (SIB)
Intraprostatic Tumor (IPT)
Proton Therapy (PT)
Androgen Deprivation Therapy (ADT)
Magnetic Resonance Imaging (MRI)
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2018-08-10
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be assigned to treatment group according to their lymph node risk or seminal vesicle invasion.

2 treatment groups:

* HR-A: Patients with \<15% risk of positive pelvic nodes, without posterior extracapsular extension and negative for seminal vesicle invasion on exam pretreatment diagnostic MRI.
* HR-B: Patient with ≥ 15% risk of positive pelvic nodes or with seminal vesicle invasion, without posterior extracapsular extension.
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to determine if dose-escalated proton radiation therapy is a good way to treat high-risk prostate cancer. The study features hypofractionation and a simultaneous integrated boost to the magnetic resonance imaging (MRI) identified intraprostatic tumor (IPT) as a method of dose-escalating radiation therapy. The study will include patients with high-risk prostate cancer who are at the highest risk for recurrence. Radiation therapy will be delivered over the course of 8-9 weeks. Additionally, androgen deprivation therapy (ADT) will be started 8-10 weeks prior to starting radiation and continued for a total of 18 months if the patient decides to receive ADT.

Detailed description: Prostate cancer is the most common noncutaneous cancer among men in the United States. The purpose of this research study is to determine if dose-escalated proton radiation therapy is a good way to treat high-risk prostate cancer.

Proton therapy (PT) is a type of ionizing radiation therapy that reduces the dose of excess radiation delivered to normal tissues. By escalating the radiation dose just to the area of the known tumor within the prostate, one could potentially reduce the amount of excess radiation delivered to surrounding organs.This reduction in dose would improve the therapeutic ratio by improving disease control while minimizing the risk for additional toxicity.

In an effort to take advantage of dose escalation's potential for improving disease control but also to limit toxicity, the use of advanced imaging to identify prostate cancer and provide a focal radiation boost to the area have proven to be useful. Recent advances in MRI have made it the most promising technique in identifying and targeting IPTs, improving both cancer control rates and decreasing toxicity.

The study features hypofractionation and a simultaneous integrated boost to the MRI identified intraprostatic tumor (IPT) as a method of dose-escalating radiation therapy. The study will include patients with high-risk prostate cancer who are at the highest risk for recurrence. Radiation therapy will be delivered over the course of 8-9 weeks. Additionally, androgen deprivation therapy (ADT) will be started 8-10 weeks prior to starting radiation and continued for a total of 18 months.

Eligibility criteria: Inclusion Criteria:

* Patient must give study-specific informed consent on an IRB-approved consent prior to any research related procedures or study treatment.
* Patient must be at least 18 years at the time of consent.
* Adenocarcinoma of the prostate with AJCC Clinical Stage T1to T3b disease with histological evaluation via biopsy or repeat biopsy within 12 months prior to registration.
* Patients must undergo a pretreatment diagnostic MRI of the prostate on a 1.5T to 3T Tesla machine within 6 months prior to study registration.
* A focal IPT must be visible on MRI within the prostate and/or seminal vesicles and this MRI must be obtained within 6 months of planning CT scan.
* A biopsy of the dominant lesion is recommended but not required. If an ultrasound guided sextant biopsy was positive for prostatic adenocarcinoma in the area of the MRI identified intraprostatic lesion, this will be acceptable and another guided biopsy targeting the MRI identified disease will not be necessary.
* Patients with at least one of the following high-risk factors: cT3a-T3b OR Gleason 9-10 OR PSA \> 30 OR more than 1 high-risk factors must be present: clinical stage of T3, Gleason score 8-10, or PSA 20 ng/ml or greater.
* Hemoglobin must be ≥ 10 g/ml within 4 months prior to registration.
* Zubrod performance status must be 0-1 within 4 months prior to registration.
* If patient has child-producing potential, they must be willing to use medically acceptable contraception during treatment and must be advised to use it for at least 1 year thereafter. This is not applicable if the patient is not sexually active or has had a vasectomy.
* Patients must be able to start treatment within 16 weeks of registration.

Exclusion Criteria:

* T4 prostate disease on CT, MRI, or physical exam.
* Patients unable to undergo MRI of the prostate.
* Patients with a greater than 25% change in prostate volume from the pretreatment MRI of the prostate demonstrating the IPT and the treatment planning MRI. Patients in this case must undergo a repeat diagnostic MRI on a 1.5T to 3.0T Tesla machine and an IPT must still be visible.
* IPT that is more than 75% of the prostate volume when measured on the CT simulation scan.
* Evidence of distant metastasis (M1).
* Patients with positive nodes on cross-sectional imaging.
* Previous prostate cancer local treatment including prostatectomy, hyperthermia, high intensity focused ultrasound, brachytherapy, external-beam radiation therapy, and/or cryotherapy.
* Prior pelvic radiation therapy.
* No prior myocardial infarction within the last 6 months, severe congestive heart failure, or end stage renal disease.
* Active inflammatory bowel disease (diverticulitis, Crohn's disease, ulcerative colitis) affecting the rectum.
* Bilateral hip replacement
* Prior intrapelvic surgery. This includes the following:

  • Bladder surgery
* Prior transurethral resection of the prostate (TURP) or laser ablation for benign prostatic hyperplasia (BPH).
* Patients receiving continuous and current anticoagulation with warfarin sodium (Coumadin), heparin sodium, clopidogrel bisulfate (Plavix), dabigatran etexilate mesylate (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa), enoxaparin sodium (Lovenox), prasugrel (Effient), ticagrelor (Brilinta), aspirin/er dipyridamole (Aggrenox), or fondaparinux sodium (Arixtra).

Primary outcomes:
measure: Cumulative rate of biochemical failure at 5 years after the end of treatment.
timeFrame: 5 years after the end of radiation therapy
Secondary outcomes:
measure: Cumulative rate of acute toxicity observed between day 1 of treatment and 90 days after treatment.
timeFrame: 90 days after the end of radiation therapy
measure: Cumulative rate of late toxicity observed between 90 days and 5 years after end of treatment.
timeFrame: 60 months after the end of radiation therapy
measure: Rate of change in sexual, bowel, and urinary function from baseline measurement to 5 years after end of treatment.
timeFrame: Rate of change between baseline measurement and 5 years end of radiation therapy
measure: Assessment of overall and disease-free survival
timeFrame: 5 years after the end of radiation therapy
measure: Assessment of local persistence or local recurrence
timeFrame: 5 years after the end of radiation therapy
measure: Rate of distant metastases five years after end of radiation therapy
timeFrame: 5 years after the end of radiation therapy
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida Health Proton Therapy Institute
state: Florida
Study officials:
affiliation: University of Florida Health Proton Therapy Institute
name: Curtis M Bryant, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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