Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02976402
Other study ID # SHARP
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date November 2016
Est. completion date November 2022

Study information

Verified date July 2019
Source Fundacao Champalimaud
Contact Manuela Seixas
Phone +351 965289072
Email manuela.seixas@fundacaochampalimaud.pt
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The present phase I trial evaluates the feasibility of a postoperative stereotactic hypofractionated external beam radiation therapy delivered in patients who underwent radical prostatectomy with adverse pathological features or early biochemical failure. Modern computer-driven technology enables the implementation of ultra-high hypofractionated Image-Guided Radiotherapy (IGRT) safely.

Eligible patients for this study are those with:

- Adenocarcinoma of the prostate treated with radical prostatectomy (any type of radical prostatectomy is permitted including retropubic, perineal, laparoscopic or robotically assisted; there is no time limit for the date of radical prostatectomy)

- Pathologic (p)T3 disease, positive margin(s), Gleason score 8-10, or seminal vesicle involvement

- Undetectable post-radical prostatectomy PSA that becomes detectable and then increases on 2 subsequent measurements (PSA of > 0.1 - ≤ 2.0 ng/mL)

- Life expectancy: 10 years

- ECOG performance status of 0 -1

- No distant metastases, based on the following workup within 60 days prior to registration

- Magnetic resonance imaging (MRI) of the pelvis

- PSMA/Choline Positron Emission Tomography (PET) to exclude systemic disease in patients with biochemical recurrence

- Patients can be on androgen deprivation therapy

- Ability to understand and willingness to sign a study-specific informed consent prior to study.

Patients enrolled in the study will undergo image-guided, volumetric intensity-modulated arc radiotherapy (IGRT-VMAT) with state-of-the-art treatment-planning and quality assurance procedures with emphasis on normal tissue sparing and delivery accuracy via the use of devices that ensure stability and beam location reproducibility.


Description:

The present study evaluates the feasibility of postoperative stereotactic hypofractionated external beam radiation therapy delivered in patients who underwent radical prostatectomy with adverse pathological features or early biochemical failure. Regardless the two settings (adjuvant or salvage), external beam radiation therapy for prostate cancer is usually a protracted course, since a total dose of 66 Gy to 70 Gy is needed to be effective. At the typical rate of 1.8 Gy to 2.0 Gy per treatment, it takes approximately 35 treatments over the course of 7 weeks to complete, which is very costly and extremely time consuming. On the other hand, the α/β ratio for prostate cancer has estimated to be as low as 1.5 Gy, significantly lower than the 3 Gy value estimated for late complications.Therefore, the delivery of the same equivalent total dose at 2 Gy/fraction (normalized total dose) to the prostate using a hypofractionation regimen, a part from the practical benefits of reducing the treatment cost and number of sessions for patients to radiotherapy departments, should have a sparing effect on early responding normal tissues through the reduction in the total dose delivered, as well as a reduction in the incidence of late complications. Trials investigating clinical and toxicity outcomes of moderate hypofractionation schedules in the curative setting have reached sufficient follow-up to show similar efficacy and toxicity to conventionally fractionated regimens.

Stereotactic body radiation therapy, or SBRT, is on the shortest end of the hypofractionation spectrum. It is accomplished in a five treatments. With its pinpoint accuracy, many Institutions currently use it for primary treatment at doses up to 9 Gy per treatment, leading to excellent outcomes at least at early time points.Patients enrolled in the study will undergo image-guided, volumetric intensity-modulated arc radiotherapy (IGRT-VMAT) with state-of-the-art treatment-planning and quality assurance procedures with emphasis 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 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 who underwent radical prostatectomy with adverse pathologic findings will be enrolled in a phase I study, consisting of 31 Gy (5 fractions of 6.2 Gy), respectively, delivered over a 1-week period at 5 fractions per week. This dosage corresponds to 68.2 Gy (for an α/βratio estimate of 1.5 Gy), compared to 52.7 Gy (for an α/β estimate of 4 Gy) in a conventional schedule. In those who developed early biochemical failure the radiation schedule will consists in 32.5 Gy (5 fractions of 6.5 Gy), respectively, delivered over a 1-week period at 5 fractions per week. This dosage corresponds to 74.3 Gy (for an α/β ratio estimate of 1.5 Gy), compared to 56.9 Gy (for an α/β estimate of 4 Gy) in a conventional schedule.

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, though not exclusively, on urinary, rectal and sexual functions and will be assessed through validated EPIC questionnaires. Serum PSA values will be drawn on the same schedule as clinical follow-up. 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 regimens, the trial will be terminated according to the standard stopping rules: >3/first 10, and >5/first 25 patients.


Recruitment information / eligibility

Status Recruiting
Enrollment 30
Est. completion date November 2022
Est. primary completion date November 2022
Accepts healthy volunteers No
Gender Male
Age group 40 Years and older
Eligibility Inclusion Criteria:

- Adenocarcinoma of the prostate treated with radical prostatectomy (any type of radical prostatectomy is permitted including retropubic, perineal, laparoscopic or robotically assisted; there is no time limit for the date of radical prostatectomy)

- Pathologic (p)T3 disease, positive margin(s), Gleason score 8-10, or seminal vesicle involvement

- Undetectable post-radical prostatectomy PSA that becomes detectable and then increases on 2 subsequent measurements (PSA of > 0.1 - = 2.0 ng/mL)

- Life expectancy: 10 years

- ECOG performance status of 0 -1

- No distant metastases, based on the following workup within 60 days prior to registration

- Magnetic resonance imaging (MRI) of the pelvis

- PSMA/Choline Positron Emission Tomography (PET) to exclude systemic disease in patients with biochemical recurrence

- Patients can be on androgen deprivation therapy

- Ability to understand and willingness to sign a study-specific informed consent prior to study entry

Exclusion Criteria:

- N1 patients are ineligible, as are those with lymph node (LN) enlargement > 1.5 cm by computed tomography (CT) or MRI of the pelvis, unless the LN is biopsy proven to be negative.

- Gross residual disease in the prostate fossa based on imaging evidence, unless biopsy proven not to contain cancer.

- Prior radiation of any kind to the prostate gland or pelvis

- Prior brachytherapy is not allowed

- History of inflammatory colitis or other active severe comorbidities

- Patients who are on immunosuppressant medication

Study Design


Intervention

Radiation:
SBRT
Postoperative RT consisting in: 31 Gy in 5 sessions each of 6.2 Gy (adjuvant intent) delivered in one week 32.5 Gy in 5 sessions each of 6.5 Gy (salvage intent) delivered in one week

Locations

Country Name City State
Portugal Champalimaud Foundation Lisboa

Sponsors (1)

Lead Sponsor Collaborator
Fundacao Champalimaud

Country where clinical trial is conducted

Portugal, 

Outcome

Type Measure Description Time frame Safety issue
Primary Feasibility (ability to deliver radiation treatment as planned). Monitoring treatment related adverse events as measured by Common Toxicity Criteria for Adverse Effects v4.0 Participants should be followed continuously, for the duration of 5 years
Secondary Number of participants with acute (= 90 days from treatment completion)treatment-related adverse events as assessed by CTCAE v4.0 Participants should be followed continuously, for the duration of 5 years
Secondary Number of participants with late (> 90 days from treatment completion) treatment-related adverse events as assessed by CTCAE v4.0 with SBRT administered to the prostate bed Participants should be followed continuously, for the duration of 5 years
Secondary Number of participants with post-treatment quality of life impairment assessed through validated tools (EPIC) Participants should be followed continuously, for the duration of 5 years
Secondary Number of participants with post-treatment abnormal laboratory values (PSA relapse) Participants should be followed continuously, for the duration of 5 years
See also
  Status Clinical Trial Phase
Terminated NCT04476797 - Phase I/II Study of SBRT and GC4711 for Centrally Located or Large NSCLC Phase 1/Phase 2
Not yet recruiting NCT04587817 - Combination of Hyperfractionated Radiotherapy With Immunotherapy in Massive Tumors
Active, not recruiting NCT04067570 - Post-Prostatectomy Linac-Based Ultrahypofractionated Radiotherapy for Patients With Localized Prostate Cancer N/A
Not yet recruiting NCT02940990 - SBRT in Multi-metastatic NSCLC Patients Which Are Pan-negative for Driver Mutations Phase 2
Terminated NCT04698915 - Phase 2b Study of GC4711 in Combination With SBRT for Nonmetastatic Pancreatic Cancer Phase 2
Active, not recruiting NCT05817604 - Stereotactic Body Radiotherapy (SBRT) for Medically Inoperable Localised Renal Tumors (SABINA Trial)
Active, not recruiting NCT04942275 - Lung Perfusion PET / CT Using Ga68-MAA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy Phase 2/Phase 3
Recruiting NCT04547452 - Combination of Sintilimab and Stereotactic Body Radiotherapy in Advanced Metastatic HCC Phase 2
Completed NCT03891472 - Clinical Phase II Clinical Study Evaluating the Toxicity and Efficacy of mFOLFIRINOX Associated With SBRT (Stereotactic Radiotherapy) in Patients With Unresectable Locally Advanced Pancreatic Cancer Phase 2
Recruiting NCT06219980 - SBRT Followed by Neoadjuvant Chemoimmunotherapy of Sindilizumab Plus Docetaxel and Cisplatin for Locoregionally Advanced Squamous Carcinoma of Oral Cavity and Oropharynx Phase 2
Recruiting NCT05344235 - Observational Study on Extreme Hypofractionation for Localized Prostate Cancer