Since high risk prostate cancer requires higher radiation, this study is being done to determine the maximum tolerated dose of radiation to the prostate and pelvic regions. Also to determine the feasibility and safety of each treatment fraction by using cone-beam Computed Tomography(CT) information and high speed Graphics Processing Unit based computation treatment planning systems. We also plan to determine the safety of treatment to the prostate. Health-related quality of life will be measured as part of current clinical practice.
- Determine the maximum tolerated dose (MTD) or to safely escalate dose to the pelvic nodal using 90 day acute toxicity endpoint
- Determine feasibility and safety of adaptive real time re-planning of the pelvic nodal region at each treatment fraction by using cone-beam CT (CBCT) information and high speed GPU based computation treatment planning systems
- Determine the safety and tolerability of 9.5 Gy per fraction in five fractions (47.5 Gy total dose) to the prostate
- Determine the feasibility and safety of temporal enhanced ultrasound for prostate lesion tracking during radiation therapy
- To follow tumor related outcomes (i.e. PSA control, progression-free survival (PFS), distant metastasis (DM) free survival, and overall survival (OS)
- Health-related quality of life (HRQOL) will be measured as part of current clinical practice Patients in each dose cohort will all be treated as a single group for dose escalation. There will be two levels of dose escalation—to prostate lesions and to pelvic lymph node region. Prostate/SV PTV will be treated at a fixed dose of 9.5 Gy per fraction for 5 fractions (47.5 Gy) based on our previous phase I/II study experiences. The starting dose for the dose escalation to the pelvic region PTV will be 4.5 Gy per fraction for 5 fractions (total dose= 22.5 Gy). Subsequent cohorts of patients will receive an additional 0.5 Gy per treatment (total 2.5 Gy per escalation). The starting dose for MRI-visible prostatic lesions will be 10 Gy and subsequent cohorts will receive an additional 0.5Gy per treatment (total of 2.5Gy per escalation).
Full Title of Study: “Phase I Clinical Trial of Stereotactic Ablative Radiotherapy (SABR) of Pelvis and Prostate Targets for Patients With High Risk Prostate Cancer”
- Study Type: Interventional
- Study Design
- Allocation: N/A
- Intervention Model: Single Group Assignment
- Primary Purpose: Treatment
- Masking: None (Open Label)
- Study Primary Completion Date: January 2022
Patients will be accrued in alternating dose levels. The two distinct areas of dose escalations (pelvic lymph node and prostate lesion) will take place one at a time. Minimum waiting periods will be assigned between each dose cohort to observe toxicity. The phase I portion of the study will be completed when dose limiting toxicity is reached or when a sufficiently high dose level (i.e.,5.5 Gy per fraction to a total 27.5 Gy for pelvic lymph node region and 11Gy per fraction to a total of 55Gy to the prostate lesion), is attained to consider the therapy likely to be efficacious. All patients will be treated with a total of 24 months of androgen suppression therapy (ADT). Radiation therapy will start 8-12 weeks after initiation of ADT.
No. Patients for each cohort: 7-15 Cohort 1: 9.5 Gy per fraction to prostate/SV, 10 Gy per fraction to prostate lesion, 4.5Gy per fraction to pelvic lymph node region for 5 fractions for a total of 47.5 / 50 / 22.5 Gy to Prostate+SV /Prostate lesions/Nodes Cohort 2: 9.5 Gy per fraction to prostate/SV, 10 Gy per fraction to prostate lesion, 5Gy per fraction to pelvic lymph node region for 5 fractions for a total of 47.5 / 50 / 25 Gy to Prostate+SV /Prostate lesions/Nodes Cohort 3: 9.5 Gy per fraction to prostate/SV, 10.5 Gy per fraction to prostate lesion, 5Gy per fraction to pelvic lymph node region for 5 fractions for a total of 47.5 / 52.5 / 25 Gy to Prostate+SV /Prostate lesions/Nodes Cohort 4: 9.5 Gy per fraction to prostate/SV, 10.5 Gy per fraction to prostate lesion, 5.5 Gy per fraction to pelvic lymph node region for 5 fractions for a total of 47.5 / 52.5 / 27.5 Gy to Prostate+SV /Prostate lesions/Nodes Cohort 5: 9.5 Gy per fraction to prostate/SV, 11 Gy per fraction to prostate lesion, 5.5 Gy per fraction to pelvic lymph node region for 5 fractions for a total of 47.5 / 55 / 27.5 Gy to Prostate+SV /Prostate lesions/Nodes
- Radiation: Stereotactic Ablative Radiotherapy
- SABR x5 fractions CBCT based image-guidance prior to each fraction: localize based on prostate/seeds positions SCORE system
Arms, Groups and Cohorts
- Experimental: Stereotactic Ablative Radiotherapy
- Stereotactic Ablative Radiotherapy (SABR)
Clinical Trial Outcome Measures
- maximum tolerated dose (MTD)
- Time Frame: 90 days
- Determine the maximum tolerated dose (MTD) or to safely escalate dose to the pelvic nodal PTV using 90 day acute toxicity endpoint
- Adverse events
- Time Frame: 90 days
- Determine the safety of 9.5 Gy per fraction in five fractions (47.5 Gy total dose) to the prostate/SV PTV
- Time Frame: 5 years
- To follow tumor response to treatment
- Progression-free survival
- Time Frame: 5 years
- To follow tumor related outcomes (progression-free survival (PFS), distant metastasis (DM) free survival)
- Overall survival
- Time Frame: 5 years
- To follow tumor related outcomes , overall survival (OS)
- Health-related quality of life
- Time Frame: 5 years
- Health-related quality of life (HRQOL) will be measured as part of current clinical practice
Participating in This Clinical Trial
- Signed study specific informed consent form.
- PSA ≥20
- OR Gleason score ≥ 8
- OR Appropriate staging studies identifying as AJCC stage cT3+
- (MR stage T3a without other high risk factors permitted at investigator discretion).
- No direct evidence of regional or distant metastases after appropriate staging studies as indicated clinically.
- Clinically negative lymph nodes as established by imaging (abdominal and pelvic CT or abdominal and pelvic MRI), nodal sampling, or dissection within 90 days prior to registration.
- Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are < 2.0 cm in the short axis.
- No distant metastases (M0) on bone scan within 90 days prior to registration.
- Histologic confirmation of cancer by biopsy
- Adenocarcinoma of the prostate
- Age ≥18
- Zubrod Performance Status 0-2
- AUA score must be ≤20 (alpha blockers allowed)
- CT or Ultrasound-based volume estimation of prostate gland ≤80 grams (repeat ultrasound measurement after hormone downsizing allowed)
- Agreement to use effective contraceptive methods such as condom/diaphragm and spermicidal foam, intrauterine device, or prescription birth control pills.
- Equivocal bone scan findings are allowed if plain films are negative for metastasis.
- Deemed eligible for Complete Androgen Blockade (CAB) hormone therapy by treating physician, including baseline liver function evaluation. For patients not eligible for anti-testosterone therapy, hormone therapy with LHRH agonist alone will be permitted on case by case basis by study P.I.
- Use of previous hormonal therapy for up to 9 months is allowed for the treatment of prostate cancer as well as for prostate volume reduction.
- MRI Pelvis/Prostate feasible for staging and planning
- Clinically eligible for rectal spacer insertion (e.g. Duraseal, SpaceOAR, or equivalent product) per physician evaluation
- Positive lymph nodes or metastatic disease from prostate cancer by imaging studies (CT or MRI), unless biopsy proven to be negative.
- Evidence of metastatic disease by imaging study
- Prior invasive malignancy unless disease free for a minimum of 3 years (oral cavity, or non-melanomatous skin cancer are all permissible)
- Previous pelvic radiotherapy
- Previous surgery or chemotherapy for prostate cancer
- Previous transuretheral resection of the prostate (TURP) or cryotherapy to the prostate
- Previous androgen depravation therapy given for more than 9 months prior to therapy
- Concomitant antineoplastic therapy (including surgery, cryotherapy, conventionally fractionated radiotherapy, and chemotherapy) while on this protocol.
- History of Crohn's Disease or Ulcerative Colitis.
- Not actively on immunosuppressive medications.
- Previous significant obstructive symptoms; AUA score must be ≤20 (alpha blockers allowed)
- Significant psychiatric illness
- Men of reproductive potential may not participate unless they agree to use an effective contraceptive method.
- Ultrasound or CT estimate of prostate volume > 80 grams (after hormone downsizing allowed).
- Severe, active co-morbidity
- No nodal disease
- No known allergies to spacer material: Polyethylene glycol (PEG) hydrogel
Gender Eligibility: Male
Minimum Age: 18 Years
Maximum Age: 99 Years
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- University of Texas Southwestern Medical Center
- Provider of Information About this Clinical Study
- Overall Official(s)
- Raquibul Hannan, MD, Principal Investigator, University of Texas Southwestern Medical Center
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