Comparative Health Research Outcomes of NOvel Surgery in Prostate Cancer

NCT04049747 | Completed Results DMC

• 1 other identifier: 19CX5006
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 10

Brief Summary

Men diagnosed with significant cancer confined to the prostate currently undergo radical therapy directed to the whole prostate (radiotherapy or prostatectomy). These provide good cancer control but can cause significant side effects. Focal Therapy involves targeting the cancer alone, whilst leaving healthy prostate gland alone. Case series have shown similar cancer control over 5 years with a much better side effect profile. However, there have been no randomised control trials (RCTs) comparing the success in cancer control and the quality of life in patients that undergo radical therapy vs those that undergo focal therapy. Further, there is a need to assess the use of additional therapies that may improve the cancer control outcomes following focal therapy. By having a trials platform with two RCTs (CHRONOS-A and CHRONOS-B) that reflect best patient and physician preferences/ equipoise, the investigators aim to answer these questions. To improve acceptability, recruitment and compliance, the investigators have an embedded study aimed at reviewing clinician and patient perspectives and trial acceptability. CHRONOS-A will compare radical therapy to focal therapy, whilst CHRONOS-B will compare focal therapy alone to focal therapy with various therapies targeting the testosterone pathway that can shrink the cancer before it is treated. The investigators think this might improve outcomes further for men that definitely want focal therapy.

Conditions

Prostate Cancer; Non-metastatic Prostate Cancer; Prostate Adenocarcinoma

Keywords

Prostate Cancer; prostate adenocarcinoma

Outcome Measures

Primary Outcomes (6)

• Pilot: Acceptance of Randomisation to Allocated Arm Within CHRONOS A & CHRONOS B

  To assess the acceptance of randomisation to the allocated arm within CHRONOS A \& CHRONOS B separately using rates of compliance, and rates of withdrawal

  12 months

• Pilot: Recruitment Rate to CHRONOS A & CHRONOS B and Their Corresponding 95% Confidence Intervals

  To estimate the recruitment rate to CHRONOS A \& CHRONOS B and their corresponding 95% confidence intervals The recruitment rate is defined as number recruited (consented) over total number of patients approached.

  12 months

• Pilot: Treatment Compliance to CHRONOS - A

  To determine the treatment compliance of patients to receiving the treatment they have been allocated to through randomisation within CHRONOS A only and corresponding 95% confidence interval. CHRONOS B results provided in a separate table

  12 months

• Pilot: Treatment Compliance (CHRONOS-B)

  To determine the treatment compliance of patients to receiving the treatment they have been allocated to through randomisation within CHRONOS B only and corresponding 95% confidence interval CHRONOS A results provided in a separate table

  12 months

• Drug Compliance to CHRONOS-B Only

  To determine patients drug compliance to allocated IMP treatment within randomisation of CHRONOS-B Arm 4 and Arm 5 only as CHRONOS -B Arm 3 is non-IMP. CHRONOS Arm A is not included as both arms are non-IMP

  12 months

• Pilot: Randomisation Rate to CHRONOS A & CHRONOS B and Their Corresponding 95% Confidence Intervals

  To estimate the randomisation rate to CHRONOS A \& CHRONOS B and their corresponding 95% confidence intervals The Randomisation rate is defined as number of randomised patients over total number of patients recruited (consented)

  12 months

Study Arms (5)

CHRONOS A - Arm 1 (Control)

EXPERIMENTAL

Radical therapy (radiotherapy or prostatectomy \[radiotherapy can be external beam or brachytherapy\]). In patients undergoing radiotherapy a maximum of 6-months neo-adjuvant hormonal therapy will be allowed. In patients undergoing radical prostatectomy, cytoreduction of maximum 6 months with medication will be permissible, provided this is part of local practice.

Procedure: Radical therapy (radiotherapy or prostatectomy [radiotherapy can be external beam or brachytherapy]

CHRONOS A - Arm 2 (Intervention)

EXPERIMENTAL

Focal therapy alone (high intensity focused ultrasound \[HIFU\] or cryotherapy as per physician and centre choice). A second focal therapy session in-field, or a first focal therapy session to an out-of-field progressive or de novo lesion will be allowed as part of the focal therapy intervention.

Procedure: Focal therapy

CHRONOS B - Arm 3 (Control)

EXPERIMENTAL

Focal therapy alone (high intensity focused ultrasound \[HIFU\] or cryotherapy as per physician and centre choice). A second treatment in-field, or a first focal ablation to an out-of-field progressive or de novo lesion will be allowed but will be regarded as failure events for the purpose of CHRONOS-B.

Procedure: Radical therapy (radiotherapy or prostatectomy [radiotherapy can be external beam or brachytherapy]

CHRONOS B - Arm 4 (Intervention):

EXPERIMENTAL

Neoadjuvant finasteride 5mg once daily for a minimum of 12 weeks followed by focal therapy (as per CHRONOS B control arm).

Procedure: Focal therapy after Finasteride 5Mg tablets for 12 weeks

CHRONOS B - Arm 5 (Intervention)

EXPERIMENTAL

Neoadjuvant bicalutamide 50mg once daily therapy for a minimum of 12 weeks followed by focal therapy (as per control arm).

Procedure: Focal therapy after Bicalutamide 50Mg tablets for 12 weeks

Interventions

Radical therapy (radiotherapy or prostatectomy [radiotherapy can be external beam or brachytherapy] PROCEDURE

Radical therapy (radiotherapy or prostatectomy \[radiotherapy can be external beam or brachytherapy\]

Also known as: radiotherapy, prostatectomy, external beam radiotherapy, brachytherapy

CHRONOS A - Arm 1 (Control); CHRONOS B - Arm 3 (Control)

Focal therapy PROCEDURE

Focal therapy (high intensity focused ultrasound or cryotherapy)

Also known as: high intensity focused ultrasound, cryotherapy, HIFU

CHRONOS A - Arm 2 (Intervention)

Focal therapy after Finasteride 5Mg tablets for 12 weeks PROCEDURE

finasteride 5mg tablets 12 weeks prior to focal therapy

Also known as: Neoadjuvant

CHRONOS B - Arm 4 (Intervention):

Focal therapy after Bicalutamide 50Mg tablets for 12 weeks PROCEDURE

Bicalutamide 50mg per day - 12 weeks prior to focal therapy

Also known as: Neoadjuvant

CHRONOS B - Arm 5 (Intervention)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PSA \</=20ng/ml
• Patients must have undergone a diagnostic pre-biopsy MRI compliant with national uro-radiology consensus guidelines. Dynamic contrast enhancement using gadolinium is not required at diagnostic stage. However, contrast enhancement MRI will be required in those men who undergo focal therapy prior to focal therapy as a baseline for comparison during follow-up. In the absence of a compliant MRI (for clinical or other reasons), a transperineal template mapping biopsy using a 5-10 mm sampling frame will be required
• Histologically proven prostate adenocarcinoma
• Overall Gleason score of 7 (either 3+4=7 or 4+3=7) of any length or Gleason 3+3=6 provided \>/=6mm cancer core length in any one core. Patients with Gleason 4+4=8 in some cores but where the overall Gleason score is 7 will be included.
• Bilateral histologically proven prostate cancer is permissible provided the following criteria are met:
• The index lesion to be treated if focal therapy is used meets the above histological criteria.
• The patient may have a PIRADS or Likert score 3, 4, 5 mpMRI lesion on the same hemi-gland (either right/left or anterior/posterior) as the histological index lesion
• Secondary areas of Gleason 3+3=6 of \</=5mm cancer outside of the treatment field can be monitored, if present, and patient undergoes focal therapy.
• If a Likert or PIRADS score 3,4 or 5 mpMRI lesion is present in an area outside of the treatment field with a negative biopsy for cancer then pathology must be reviewed and confirm the presence of inflammation or atrophy if the patient is to undergo focal therapy\*
• Radiological stage T2b/T3a will require central review regarding suitability for focal therapy.
• Index tumour volume, as seen on mpMRI if carried out, will be restricted to 50% of one lobe for either unilateral or bilateral ablation, patients with tumour volume \>/=50% of one lobe will require central review prior to enrolment. Final decisions on suitability of focal therapy will lie with the trial central review in these cases.
• No restriction exists in CHRONOS-A on previous or current use of 5-alpha reductase inhibitors or anti-androgens or LHRH agonists or LHRH antagonists.
• Age at least 18 years of age
• Participants must be fit to undergo all procedures listed in the protocol as judged by clinical team

You may not qualify if:

• Previous or current LHRH agonist or LHRH antagonist or anti-androgen use in CHRONOS-B.
• Patients already established on a 5 alpha-reductase inhibitor (finasteride or dutasteride) who wish to go into CHRONOS-B will need to discontinue this for at least 6 months prior to randomisation. (NB: testosterone supplementation is permitted)
• Previous treatment for prostate cancer
• Life expectancy is likely to be less than 10 years
• Unable to give informed consent

Sponsors & Collaborators

• Imperial College London: lead
• Prostate Cancer UK: collaborator
• Imperial Clinical Trials Unit (ICTU): collaborator

Study Sites (10)

King's College Hospital NHS Foundation Trust

Brixton, London, SE5 9RS, United Kingdom

Location

West Middlesex Hospital

Isleworth, Middlesex, TW7 6AF, United Kingdom

Location

Newcastle upon Tyne Hospitals NHS Foundation Trust

High Heaton, Newcastle Upon Tyne, NE7 7DN, United Kingdom

Location

Ashford & St Peter's Hospitals (ASPH) NHS Foundation Trust

Chertsey, Surrey, KT16 0PZ, United Kingdom

Location

Hampshire Hospital NHS Foundation Trust

Basingstoke, RG24 9NA, United Kingdom

Location

Kingston Hospital NHS Foundation Trust

Kingston upon Thames, KT2 7QB, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

South Tyneside and Sunderland NHS Foundation Trust

Sunderland, United Kingdom

Location

Related Publications (1)

• Reddy D, Shah TT, Dudderidge T, McCracken S, Arya M, Dobbs C, Emberton M, Fiorentino F, Day E, Prevost AT, Staffurth J, Sydes M, Winkler M, Ahmed HU. Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS): A prospective, multi-centre therapeutic phase II parallel Randomised Control Trial. Contemp Clin Trials. 2020 Jun;93:105999. doi: 10.1016/j.cct.2020.105999. Epub 2020 Apr 14.

  PMID: 32302790 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiotherapy; Prostatectomy; Brachytherapy; Cryotherapy; WW Domain-Containing Oxidoreductase; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Urologic Surgical Procedures, Male; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Combined Modality Therapy

Results Point of Contact

• Title: Ms Puja Jadav
• Organization: Imperial College London

p.jadav@imperial.ac.uk

020 7594 7773

Study Officials

• Hashim Ahmed

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two linked Randomised Controlled Trials with CHRONOS-A and CHRONOS-B discussed with patients and choice of A or B dependent on physician and patient equipoise. * CHRONOS-A Two arm RCT * CHRONOS-B Multi-Arm Multi-Stage (MAMS) Randomised Control Trial

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: August 8, 2019
• Study Start: December 11, 2019
• Primary Completion: March 20, 2023
• Study Completion: March 20, 2023
• Last Updated: March 24, 2025
• Results First Posted: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (10)