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Comparative Health Research Outcomes of NOvel Surgery in Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04049747
Recruitment Status : Recruiting
First Posted : August 8, 2019
Last Update Posted : February 12, 2020
Sponsor:
Collaborators:
Prostate Cancer UK
Imperial Clinical Trials Unit (ICTU)
Information provided by (Responsible Party):
Imperial College London

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.


Condition or disease Intervention/treatment Phase
Prostate Cancer Non-metastatic Prostate Cancer Prostate Adenocarcinoma Procedure: Radical therapy (radiotherapy or prostatectomy [radiotherapy can be external beam or brachytherapy] Procedure: Focal therapy Procedure: Focal therapy after Finasteride 5Mg tablets for 12 weeks Procedure: Focal therapy after Bicalutamide 50Mg tablets for 12 weeks Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Imperial Prostate 4: Comparative Health Research Outcomes of NOvel Surgery in Prostate Cancer
Actual Study Start Date : December 11, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : May 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: CHRONOS A - Arm 1 (Control)
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]
Radical therapy (radiotherapy or prostatectomy [radiotherapy can be external beam or brachytherapy]
Other Names:
  • radiotherapy
  • prostatectomy
  • external beam radiotherapy
  • brachytherapy

Experimental: CHRONOS A - Arm 2 (Intervention)
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
Focal therapy (high intensity focused ultrasound or cryotherapy)
Other Names:
  • high intensity focused ultrasound
  • cryotherapy
  • HIFU

Experimental: CHRONOS B - Arm 3 (Control)
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]
Radical therapy (radiotherapy or prostatectomy [radiotherapy can be external beam or brachytherapy]
Other Names:
  • radiotherapy
  • prostatectomy
  • external beam radiotherapy
  • brachytherapy

Experimental: CHRONOS B - Arm 4 (Intervention):
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
finasteride 5mg tablets 12 weeks prior to focal therapy
Other Name: Neoadjuvant

Experimental: CHRONOS B - Arm 5 (Intervention)
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
Bicalutamide 50mg per day - 12 weeks prior to focal therapy
Other Name: Neoadjuvant




Primary Outcome Measures :
  1. Acceptance of randomisation to allocated arm within CHRONOS A & CHRONOS B [ Time Frame: 12 months ]
    To assess the acceptance of randomisation to the allocated arm within CHRONOS A & CHRONOS B using rates of compliance, and rates of withdrawal

  2. CHRONOS-A Primary Outcome Measures - progression-free survival (PFS) rates of focal therapy alone compared to radical therapy. [ Time Frame: 60 months ]
    To evaluate progression-free survival (PFS) rates of focal therapy alone compared to radical therapy (radiotherapy or surgery) in the treatment of non-metastatic clinically significant prostate cancer. PFS is defined as time from randomisation to salvage whole-gland or systemic therapy, prostate cancer metastases or prostate cancer-specific mortality.

  3. CHRONOS-B Primary Outcome Measures - Failure-Free-Survival (FFS) rates of focal therapy alone compared to focal therapy combined with other therapies. [ Time Frame: 60 months ]
    To evaluate Failure-Free-Survival (FFS) rates of focal therapy alone compared to focal therapy combined with other therapies as a neoadjuvant strategy. FFS is defined as time from randomisation to further focal therapy session or salvage whole-gland or systemic therapy or prostate cancer metastases or prostate cancer-specific mortality.


Secondary Outcome Measures :
  1. Progression (Biochemical / Radiological / Clinical) [ Time Frame: 60 months ]
    Progression on PSA and imaging and impact of clinical features on progression, measured using PSA blood tests

  2. Frequency of adverse events as determined by Common Terminology Criteria for Adverse Events. [ Time Frame: 60 months ]
    To observe the frequency of adverse events as determined by Common Terminology Criteria for Adverse Events.

  3. Health-related quality-of-life [ Time Frame: 60 months ]
    Health-related quality-of-life, measured using EuroQol (EQ-5D-5L) questionnaire, Score 0-100

  4. Urinary side effects, IPSS questionnaire [ Time Frame: 60 months ]
    Urinary side effects, measured using the IPSS questionnaire, Score 0-35

  5. Urinary side effects, EPIC-Urinary domain questionnaire [ Time Frame: 60 months ]
    Urinary side effects, measured using the EPIC-Urinary domain questionnaire, Score 0-34

  6. Sexual side effects [ Time Frame: 60 months ]
    Sexual side effects, measured using the IIEF15 questionnaire, Score 0-75.

  7. Effect on quality of life [ Time Frame: 60 months ]
    Effect on quality of life, measured using the EPIC - 26 questionnaire, Score 0-79

  8. Impact of participants' overall health-related quality assessed by validated patient reported outcomes measures [ Time Frame: 60 months ]
    To observe the impact of participants' overall health-related quality- of- life as well as adverse events and impact on genito-urinary and rectal functional status using validated patient reported outcomes measures (International Index of Erectile Function-15, EPIC-26, EPIC Urinary domain, International Prostate Symptom Score and CTCAEv4.0 bowel domain). Further analysis to be performed using qualitative interview datasets in a multi-methods analysis.

  9. Comparison of predictive value of different MRI scoring systems against histological outcomes. [ Time Frame: 60 months ]
    To compare the predictive value of the PI-RADS and/or Likert scoring system against histological outcomes in patients treated with localised, clinically significant prostate cancer over at least 5 years.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04049747


Contacts
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Contact: Hashim Ahmed 0203 311 1673 hashim.ahmed@imperial.ac.uk
Contact: Thiagarajah Sasikaran, PhD 0207 594 6017 t.sasikaran@imperial.ac.uk

Locations
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United Kingdom
Ashford & St Peter's Hospitals (ASPH) NHS Foundation Trust Recruiting
Chertsey, Surrey, United Kingdom, KT16 0PZ
Contact: Nimalan Arumainayagam         
Principal Investigator: Nimalan Arumainayagam         
Imperial College Healthcare NHS Trust Recruiting
London, United Kingdom, W6 8RF
Contact: Hashim U Ahmed, BM, BCh (Oxon), BA, PhD, FRCS       hashim.ahmed@imperial.ac.uk   
The Royal Marsden NHS Foundation Trust Not yet recruiting
London, United Kingdom
Contact: Vincent Khoo         
Principal Investigator: Vincent Khoo         
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, United Kingdom
Contact: Tim Dudderidge         
Principal Investigator: Tim Dudderidge, FRCS (Urol)         
South Tyneside and Sunderland NHS Foundation Trust Recruiting
Sunderland, United Kingdom
Contact: Stuart McCracken         
Principal Investigator: Stuart McCracken, FRCS (Urol)         
Sponsors and Collaborators
Imperial College London
Prostate Cancer UK
Imperial Clinical Trials Unit (ICTU)
Investigators
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Principal Investigator: Hashim Ahmed Imperial College London
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT04049747    
Other Study ID Numbers: 19CX5006
First Posted: August 8, 2019    Key Record Dates
Last Update Posted: February 12, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Imperial College London:
Prostate Cancer
prostate adenocarcinoma
Additional relevant MeSH terms:
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Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Bicalutamide
Finasteride
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
5-alpha Reductase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents