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

Primary Purpose

Prostate Cancer

Status

Active

Phase

Phase 2

Locations

Ireland

Study Type

Interventional

Intervention

questionnaire administration

quality-of-life assessment

image-guided radiation therapy

intensity-modulated radiation therapy

radiation therapy treatment planning/simulation

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

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)
Only patients requiring neo-adjuvant / adjuvant hormonal therapy will be included in this study
Absence of distant metastases as demonstrated by history and physical examination, FBC, screening profile including liver function tests, PSA and bone scan
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.
No previous surgery for urinary conditions except TURP or TRUS
KPS > or equal to 60
Age >18 years
Provision of written informed consent in line with ICH-GCP guidelines

Exclusion Criteria:

Previous RT to the pelvic region
The patient has nodal involvement or it is decided to electively treat pelvic lymph nodes
The patient has had a bilateral orchidectomy
The patient has previously received a full course of hormonal treatment for his prostate cancer
The patient has or has had other malignancies within the last 5 years (non-melanoma skin cancer is permitted)
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
Patients who have had a prostatectomy
The presence of hip prostheses

Sites / Locations

Cork University Hospital
SLRON St Luke's Hospital
Beacon Hospital
SLRON St James's Hospital
SLRON, Beaumont Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Arm A

Arm Description

Treatment will be delivered in 1.8 Gy fractions; dose escalation will be in 1.8 Gy increments from 75.6 Gy to a maximum 81 Gy.

Outcomes

Primary Outcome Measures

Biochemical Failure Free survival

Secondary Outcome Measures

Overall survival and disease free survival rates

Maximum dose escalation

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.

Full Information

NCT ID

NCT00951535

First Posted

August 1, 2009

Last Updated

April 5, 2023

Sponsor

Cancer Trials Ireland

1. Study Identification

Unique Protocol Identification Number

NCT00951535

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

July 20, 2009 (Actual)

Primary Completion Date

October 2023 (Anticipated)

Study Completion Date

October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cancer Trials Ireland

4. Oversight

5. Study Description

Brief 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).

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

251 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Other

Arm Description

Treatment will be delivered in 1.8 Gy fractions; dose escalation will be in 1.8 Gy increments from 75.6 Gy to a maximum 81 Gy.

Intervention Type

Other

Intervention Name(s)

questionnaire administration

Intervention Type

Procedure

Intervention Name(s)

quality-of-life assessment

Intervention Type

Radiation

Intervention Name(s)

image-guided radiation therapy

Intervention Type

Radiation

Intervention Name(s)

intensity-modulated radiation therapy

Intervention Type

Radiation

Intervention Name(s)

radiation therapy treatment planning/simulation

Primary Outcome Measure Information:

Title

Biochemical Failure Free survival

Time Frame

7-9 years median follow-up

Secondary Outcome Measure Information:

Title

Overall survival and disease free survival rates

Time Frame

5-7 years follow-up

Title

Maximum dose escalation

Time Frame

9 years follow-up

Title

Time Frame

9 years follow-up

Other Pre-specified Outcome Measures:

Title

Identify prognostic and biochemical markers of early disease progression (Sub-Study 1)

Description

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.

Time Frame

9 years follow-up

Title

Develop a platform for endpoint prediction using Raman spectroscopy and machine learning (Sub-Study 2)

Description

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.

Time Frame

9 years follow-up

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Only patients requiring neo-adjuvant / adjuvant hormonal therapy will be included in this study Absence of distant metastases as demonstrated by history and physical examination, FBC, screening profile including liver function tests, PSA and bone scan 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. No previous surgery for urinary conditions except TURP or TRUS KPS > or equal to 60 Age >18 years Provision of written informed consent in line with ICH-GCP guidelines Exclusion Criteria: Previous RT to the pelvic region The patient has nodal involvement or it is decided to electively treat pelvic lymph nodes The patient has had a bilateral orchidectomy The patient has previously received a full course of hormonal treatment for his prostate cancer The patient has or has had other malignancies within the last 5 years (non-melanoma skin cancer is permitted) 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 Patients who have had a prostatectomy The presence of hip prostheses

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Gerard Armstrong, MD, MB, MRCPI

Organizational Affiliation

SLRON St Luke's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cork University Hospital

City

Cork

Country

Ireland

Facility Name

SLRON St Luke's Hospital

City

Dublin

ZIP/Postal Code

Country

Ireland

Facility Name

Beacon Hospital

City

Dublin

Country

Ireland

Facility Name

SLRON St James's Hospital

City

Dublin

Country

Ireland

Facility Name

SLRON, Beaumont Hospital

City

Dublin

Country

Ireland

12. IPD Sharing Statement

Citations:

PubMed Identifier

28001146

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.

Results Reference

background

PubMed Identifier

31269684

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.

Results Reference

background

PubMed Identifier

28764689

Citation

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.

Results Reference

background

PubMed Identifier

29528761

Citation

Meade AD, Maguire A, Bryant J, Cullen D, Medipally D, White L, McClean B, Shields L, Armstrong J, Dunne M, Noone E, Bradshaw S, Finn M, Shannon AM, Howe O, Lyng FM. Prediction of DNA damage and G2 chromosomal radio-sensitivity ex vivo in peripheral blood mononuclear cells with label-free Raman micro-spectroscopy. Int J Radiat Biol. 2019 Jan;95(1):44-53. doi: 10.1080/09553002.2018.1451006. Epub 2018 Mar 29.

Results Reference

derived

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

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