Clinical trial NCT03169933: Combined, Intensified and Modulated Adjuvant Therapy in Prostate Carcinoma
Official title: Combined, Intensified and Modulated Adjuvant Therapy in Prostate Carcinoma: a Phase II Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prostate Cancer
Keywords: adjuvant
androgen suppressive therapy
literature review
phase II
prostate neoplasms
radiotherapy
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
Collaborators: name: Catholic University of the Sacred Heart
name: Howard University
name: University of Bologna
name: Michigan State University
First posted: 2017-05-30
Enrollment: 123
Sex: MALE
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients with high risk prostate cancer may benefit from radiotherapy after radical prostatectomy. The investigators postulated that adjuvant androgen deprivation therapy (ADT), radiation dose escalation, and selective pelvic irradiation may improve outcome. A phase II trial was designed to prove that combined-intensified-modulated-adjuvant (CIMA) treatment may improve 5-year biochemical relapse free survival (bRFS) from 75% to 90% in high risk patients. The delivered dose to tumor bed and pelvic nodes was 64.8-70.2 Gy and 45 Gy (57% of patients), respectively, and 69% received ADT.

Detailed description: Prostate cancer patients at high risk of loco-regional recurrences may benefit from postoperative radiotherapy (RT) following radical prostatectomy (EORTC trial 22911). However, despite an improvement in biochemical relapse-free survival (bRFS), the risk of recurrences remained high for those patients. The investigators postulated that adjuvant androgen deprivation therapy (ADT), radiation dose escalation, and selective pelvic irradiation for patients at risk for regional failures may improve the outcome. The combined-intensified-modulated-adjuvant (CIMA) as described may improve survival through a reduction of loco-regional and systemic failures.

A phase II trial was designed to test the hypothesis that CIMA treatment may improve 5-year bRFS by 15%. Patients less than 80 years old, with a histological diagnosis of prostate adenocarcinoma without distant metastases, stage pT2-4 N0-1, no previous treatments and an ECOG performance status of 0-2 were selected. All patients had at least one of these pathologic features: extracapsular extension, positive surgical margins, or seminal vesicle invasion. Radiation dose to the tumor bed ranged from 64.8 to 70.2 Gy. Pelvic lymph nodes were treated to 45 Gy in selected patients at risk of regional failures (57%). Selected patients at risk for distant metastases (69.1%) received hormonal therapy.

Eligibility criteria: Inclusion Criteria:

* \< 80 years old
* histological diagnosis of prostate adenocarcinoma
* no distant metastases
* stage pT2-4
* N0-1
* ECOG performance status of 0-2
* One of these pathologic features: extracapsular extension, positive surgical margins, or seminal vesicle invasion. extracapsular extension, positive surgical margins or seminal vesicle invasion, or positive lymph-nodes
* No surgical complications such as pelvic infections or lymphocele, intraoperative rectal injury or severe urinary incontinence
* Preoperative and postoperative PSA test, bone scan and CT-scan or MRI of abdomen and pelvis prior to enrolment
* Normal bone marrow function

Exclusion Criteria:

* Previously treated with Radiotherapy
* Previously treated with androgen deprivation therapy
* Previously treated with chemotherapy for prostate cancer. They also had to be free

Primary outcomes:
measure: Biochemical relapse free survival
timeFrame: Five years
Secondary outcomes:
measure: Incidence of early treatment-emergent adverse events
timeFrame: < 90 days.
measure: Incidence of late treatment-emergent adverse events were assessed with Radiation Morbidity Scoring Scheme of the RTOG/European Organization for Research and Treatment of Cancer (EORT)
timeFrame: 5 years
measure: First evidence of any pelvic recurrence
timeFrame: 5 years
measure: Metastasis-free survival
timeFrame: 5 years
Other outcomes:
Locations:
Study officials:
affiliation: Radiation Oncology Center, Department of Experimental, Diagnostic and Speciality Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
name: Alessio G Morganti, MD
role: STUDY_DIRECTOR
References:
citation: Mantini G, Siepe G, Alitto AR, Buwenge M, Nguyen NP, Farioli A, Schiavina R, Catucci F, Deodato F, Fionda B, Frascino V, Macchia G, Ntreta M, Padula GDA, Arcelli A, Cammelli S, Rambaldi GZ, Cilla S, Valentini V, Morganti AG. Tailored postoperative treatment of prostate cancer: final results of a phase I/II trial. Prostate Cancer Prostatic Dis. 2018 Nov;21(4):564-572. doi: 10.1038/s41391-018-0064-7. Epub 2018 Jul 23.