A Prospective Phase II Dose Escalation Study Using IMRT for High Risk N0 M0 Prostate Cancer. ICORG 08-17

Prostate Cancer Clinical Trial

Official title:

A Prospective Phase II Dose Escalation Study Using IMRT for High Risk N0M0 Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00951535
• Other study ID #: 08-17 ICORG
• Secondary ID: CTRIAL-IE 08-17
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 20, 2009
• Est. completion date: October 2025

Study information

• Verified date: April 2023
• Source: Cancer Trials Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, phase II non-randomised controlled clinical study. Dose escalation will be implemented using 1.8 Gy increments from baseline 75.6 Gy. Patients' RT prescription may be escalated up to max 81 Gy once dose volume constraints are adhered to.

All patients will be treated using the participating institution's standard rectal preparation protocol, bladder-filling protocol and appropriate immobilisation device(s).

Cone beam CT on-treatment imaging is recommended for this study. However, the use of individual institutional imaging equipment and techniques is permitted.

Acute GU/GI toxicities will be assessed weekly during treatment.

GU/GI toxicities will also be assessed 2 months post RT, 8 months post RT and 6 monthly thereafter to year nine and in line with the participating institution's standard routine follow-up (FU) thereafter.

Translational sub-studies (optional), only apply to patients who are consented prior to commencement of hormone therapy at centres participating in the translational sub-study. Patients at centres participating in the translational sub-studies will be given the option of participating in sub-study 1 (Proteomic Analysis), sub-study 2 (Raman spectroscopic analysis), or both (sample collection will not be mandatory).

Description:

Primary Objective:

To determine if dose escalated IMRT for high risk localised prostate cancer can provide PSA relapse free survival similar to that reported by Memorial Sloan Kettering (Alicikus et al 2011).

Sub-Study 1 (Proteomic Analysis):

To use proteomic analysis of sequential blood and urine samples to detect changes in profiles that may predict outcome and identify prognostic biochemical markers of early disease progression and/ or toxicity. The unique molecular signatures may also allow the identification of targets for therapeutic intervention.

To undertake, where possible, other biochemical analyses including mRNA, miRNA and metabolite profiling.

Sub-Study 2 (Raman spectroscopic analysis):

To investigate a new approach to prediction of radiation response, based on biochemical fingerprinting

Secondary Objectives:

• Overall survival and disease-free survival rates.

• To evaluate the significance of published prognostic/ stratification factors such as the UCSF-CAPRA score and assess their application to the data from this study.

• To achieve the maximum dose escalation (up to 81Gy). This will be assessed as the percentage of patients that receive each dose level for all categories (dose increments of 1.8 Gy from 75.6 Gy up to max 81 Gy).

• The incidence and severity of acute and late GU, GI and erectile dysfunction toxicities will be described, and correlated with DVH parameters.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 251
• Est. completion date: October 2025
• Est. primary completion date: October 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients undergoing a radical course of RT for high-risk disease (defined according to the National Comprehensive Cancer Network Practice Guidelines in Oncology v.1 as one or more of the NCCN high risk criteria > or equal to T3, > or equal to Gleason 8, PSA > 20ng/ml)

2. Only patients requiring neo-adjuvant / adjuvant hormonal therapy will be included in this study

3. Absence of distant metastases as demonstrated by history and physical examination, FBC, screening profile including liver function tests, PSA and bone scan

4. All patients must have an MRI/CT of the prostate and pelvis to investigate the nodal status and precise T-stage. This MRI/CT scan must be performed prior to commencement of hormonal therapy. Suspicious nodes need to be histologically proven to be benign before the patient can be included in the study). M0 on staging.

5. No previous surgery for urinary conditions except TURP or TRUS

6. KPS > or equal to 60

7. Age >18 years

8. Provision of written informed consent in line with ICH-GCP guidelines

Exclusion Criteria:

1. Previous RT to the pelvic region

2. The patient has nodal involvement or it is decided to electively treat pelvic lymph nodes

3. The patient has had a bilateral orchidectomy

4. The patient has previously received a full course of hormonal treatment for his prostate cancer

5. The patient has or has had other malignancies within the last 5 years (non-melanoma skin cancer is permitted)

6. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial or if it is felt by the research/ medical team that the patient may not be able to comply with the protocol

7. Patients who have had a prostatectomy

8. The presence of hip prostheses

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Other:
• questionnaire administration

Procedure:
• quality-of-life assessment

Radiation:
• image-guided radiation therapy

• intensity-modulated radiation therapy

• radiation therapy treatment planning/simulation

Locations

Country	Name	City	State
Ireland	Cork University Hospital	Cork
Ireland	Beacon Hospital	Dublin
Ireland	SLRON St James's Hospital	Dublin
Ireland	SLRON St Luke's Hospital	Dublin
Ireland	SLRON, Beaumont Hospital	Dublin

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Trials Ireland

Country where clinical trial is conducted

Ireland, 

References & Publications (3)

Cagney DN, Dunne M, O'Shea C, Finn M, Noone E, Sheehan M, McDonagh L, O'Sullivan L, Thirion P, Armstrong J. Heterogeneity in high-risk prostate cancer treated with high-dose radiation therapy and androgen deprivation therapy. BMC Urol. 2017 Aug 1;17(1):60. doi: 10.1186/s12894-017-0250-2. — View Citation

Medipally DK, Maguire A, Bryant J, Armstrong J, Dunne M, Finn M, Lyng FM, Meade AD. Development of a high throughput (HT) Raman spectroscopy method for rapid screening of liquid blood plasma from prostate cancer patients. Analyst. 2017 Apr 10;142(8):1216-1226. doi: 10.1039/c6an02100j. — View Citation

Medipally DKR, Nguyen TNQ, Bryant J, Untereiner V, Sockalingum GD, Cullen D, Noone E, Bradshaw S, Finn M, Dunne M, Shannon AM, Armstrong J, Lyng FM, Meade AD. Monitoring Radiotherapeutic Response in Prostate Cancer Patients Using High Throughput FTIR Spectroscopy of Liquid Biopsies. Cancers (Basel). 2019 Jul 2;11(7):925. doi: 10.3390/cancers11070925. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Identify prognostic and biochemical markers of early disease progression (Sub-Study 1)	To detect changes in profiles that may predict outcome and identify prognostic and biochemical markers of early disease progression in accordance with the primary and secondary objectives using Proteomic Analysis of sequential blood and urine samples.	9 years follow-up
Other	Develop a platform for endpoint prediction using Raman spectroscopy and machine learning (Sub-Study 2)	Raman spectra will be recorded from both lymphocytes and sera to produce a library of spectral measurements in patients pre- and post-treatment. Established methodologies for the assessment of the patient radiosensitivity (G2 assay, DNA damage assays and gene expression profiling), will be used in parallel with advanced multivariate and machine learning methodologies to develop a platform for prediction of such endpoints using Raman spectra of the cellular and plasma fraction of the patient blood.	9 years follow-up
Primary	Biochemical Failure Free survival		7-9 years median follow-up
Secondary	Overall survival and disease free survival rates		5-7 years follow-up
Secondary	Maximum dose escalation		9 years follow-up
Secondary	The incidence and severity of Genito-urinary (GU), Gastro-intestinal (GI) and erectile dysfunction (ED) toxicities (graded by NCI CTCAE Version 3.0) will be analysed and correlated with dose volume histogram (DVH) parameters.		9 years follow-up