Combined, Intensified and Modulated Adjuvant Therapy in Prostate Carcinoma

Combined, Intensified and Modulated Adjuvant Therapy in Prostate Carcinoma: a Phase II Trial

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Combined, intensified and modulated adjuvant radiotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: intensified and modulated adjuvant RT; All patients underwent combined, intensified and modulated adjuvant radiotherapy for 5 days a week with the following doses: 1) pelvic node irradiation (45 Gy; 1.8 Gy/fraction) followed by boost on the prostate bed (19.8-25.2 Gy; 1.8 Gy/fraction; total dose: 64.8-70.2 Gy) or 2) exclusive prostate bed irradiation (64.8 -70.2 Gy; 1.8 Gy/fraction).	Radiation: Combined, intensified and modulated adjuvant radiotherapy; Other Names: adjuvant androgen deprivation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical relapse free survival	Survival free from increase of PSA level exceeding 0.2 ng/mL for those with postsurgical PSA level of 0.2 ng/mL or lower, and as two consecutive PSA increases for patients with a postsurgical PSA level of > 0.2 ng/ml	Five years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First evidence of any pelvic recurrence	First evidence of any pelvic recurrence	5 years
Incidence of early treatment-emergent adverse events	Adverse events after radiotherapy . Acute side effects were scored according to the Radiation Therapy Oncology Group (RTOG) scale.	< 90 days.
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)	Late complications were assessed with the Late Radiation Morbidity Scoring Scheme of the RTOG/European Organization for Research and Treatment of Cancer (EORT)	5 years
Metastasis-free survival	The first evidence of any extra pelvic recurrence of disease.	5 years

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Collaborators: University of Bologna; Catholic University of the Sacred Heart; Michigan State University; Howard University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 2, 2004
• Primary Completion (ACTUAL): January 10, 2009
• Study Completion (ACTUAL): January 2, 2017

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: May 25, 2017
• First Posted (ACTUAL): May 30, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 6, 2018
• Last Update Submitted That Met QC Criteria: March 5, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: radiotherapy; adjuvant; phase II; prostate neoplasms; androgen suppressive therapy; literature review
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens
• Other Study ID Numbers: CIMA-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No