Biomarker-driven Intermittent Docetaxel Versus Standard-of-care (SOC) Docetaxel in Metastatic Castration-resistant Prostate Cancer (GUIDE)

A Randomised Non-comparative Phase II Trial of Biomarker-driven Intermittent Docetaxel Versus Standard-of-care (SOC) Docetaxel in Metastatic Castration-resistant Prostate Cancer (mCRPC)

The purpose of this study is to see if a prostate cancer marker in the blood (mGSTP1) can be used to guide chemotherapy treatment. Based on the level of this blood marker, some men may be able to have breaks in treatment rather than having chemotherapy continuously which is the current standard of care. This study will tell us if having these treatment breaks guided by mGSTP1 can improve how men feel during treatment while still treating the prostate cancer effectively.

Docetaxel is a chemotherapy drug that is approved to treat prostate cancer and has been used for many years to treat prostate cancer like yours. Your doctor has already discussed this with you and you have both agreed that docetaxel is the best treatment for you to have at this time. You will have already started this chemotherapeutic treatment with docetaxel.

Study Overview

• Status: Recruiting
• Conditions: Castration Resistant Prostatic Cancer
• Intervention / Treatment: Drug: Docetaxel intermittent; Drug: Docetaxel standard of care

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ronan Burder; Phone Number: 03 8559 5088; Email: ronan.burder@petermac.org
• Study Contact Backup: Name: Margaret McJannett; Phone Number: 02 9562 5033; Email: margaret@anzup.org.au

Study Locations

• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2460
      • Recruiting
      • Border Medical Oncology Research Unit / The Border Cancer Hospital
      • Contact: Craig Underhill; Email: cunderhill@bordermedonc.com.au
      • Contact: Jacqui McBurnie; Phone Number: +61 2 6064 1508; Email: jacqui.mcburnie@bordermedonc.com.au
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris O'Brien Lifehouse
      • Contact: Jacquie Harvey
      • Principal Investigator: Kate Mahon
    • Darlinghurst, New South Wales, Australia, 2021
      • Recruiting
      • St Vincent's Hospital
      • Principal Investigator: Megan Crumbaker
    • Dubbo, New South Wales, Australia, 2830
      • Recruiting
      • Dubbo Base Hospital
      • Contact: Florian Honeyball
      • Contact: Alicia Bell
      • Principal Investigator: Florian Honeyball
    • Sydney, New South Wales, Australia
      • Recruiting
      • Concord Repatriation General Hospital
      • Principal Investigator: Martin Stockler
      • Contact: Karen Ji
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Recruiting
      • Frankston Hospital-Peninsula Health
      • Contact: Jade Rice
      • Principal Investigator: Sanjeev Seewak
    • Shepparton, Victoria, Australia, 3630
      • Recruiting
      • Goulburn Valley Health
      • Contact: Javier Torres; Email: javier.torres@gvhealth.org.au
      • Contact: Carole Mott
    • Traralgon, Victoria, Australia, 3844
      • Not yet recruiting
      • Latrobe Regional Hospital
      • Contact: Jhodie Duncan
      • Principal Investigator: Hieu Chau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

PRESCREENING INCLUSION CRITERIA

1. Patient has provided written informed consent using the GUIDE pre-screening PICF
2. Age ≥ 18 years at the time of pre-screening consent
3. Males with metastatic castration-resistant prostate cancer (as per PCWG3) AND are planned to commence docetaxel chemotherapy
4. WHO Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 1)
5. Histological confirmation of prostate cancer

6. Patients must have adequate bone marrow and hepatic function within 14 days prior Cycle 1 day 1:

   • Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last 4 weeks)
   • Platelets ≥ 100 x 109/L
   • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
   • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
   • Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) ≤ 2.5 x ULN
7. Willing and able to comply with all pre-screening study requirements, including blood tests for mGSTP1 analysis before and during docetaxel treatment

PRESCREENING EXCLUSION CRITERIA

1. Prior docetaxel or cabazitaxel chemotherapy for castration-resistant prostate cancer
2. Prior docetaxel in the castration sensitive prostate cancer setting within the previous 2 years
3. Known hypersensitivity to docetaxel or its excipients
4. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
5. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol

MAIN SCREENING INCLUSION CRITERIA

1. Patient has provided written informed consent for the main GUIDE study PICF
2. Patient has a detectable plasma mGSTP1 deoxyribonucleic acid (DNA) as measured by central laboratory at prescreening prior to commencing first cycle of docetaxel chemotherapy
3. Patient has commenced 3 cycles of docetaxel
4. Patient has undetectable plasma mGSTP1 DNA as measured by central laboratory from blood taken prior to the third cycle of docetaxel
5. Patient is willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.

MAIN SCREENING EXCCLUSION CRITERIA

1. Known hypersensitivity to docetaxel or its excipients
2. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
3. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
4. Progressive disease by RECIST 1.1 within the first 3 cycles of docetaxel

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Intermittent docetaxel treatment; suspend docetaxel prior to cycle 4, recommencement based on mGSTP1 monitoring	Drug: Docetaxel intermittent; After 3 cycles of docetaxel chemotherapy (75mg/m^2 every 21) in combination with an undetectable mGSTP1 level, patients randomised to this arm will stop docetaxel treatment. Plasma mGSTP1 is measured every 21 days and docetaxel treatment will be recommenced if it mGSTP1 becomes detectable again.
Active Comparator: Arm 2: Standard of Care docetaxel treatment; Docetaxel administered as per Standard of Care: as per clinician recommendation	Drug: Docetaxel standard of care; After 3 cycles of docetaxel chemotherapy (75mg/m^2 every 21) in combination with an undetectable mGSTP1 level, patients randomised to this arm will continue with standard Docetaxel treatment (75mg/m^2 every 21)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression free survival (rPFS)	Radiographic progression free survival (rPFS) is defined as the time from randomisation (i.e. prior to cycle 4), the date of first documented progression on imaging by site investigator (PCWG3 criteria for bone lesions and RECIST 1.1 for soft tissue lesions) or death due to any cause.	From randomisation until last patient has completed 2 years in follow up, on average 3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time on treatment holidays	Time on treatment holidays is defined as the total length of time patients on the intermittent docetaxel arm spend off docetaxel within the treatment period i.e. prior to permanent treatment discontinuation	From randomisation until last patient has completed 2 years in follow up, on average 3.5 years
Overall treatment safety	Incidence and severity of adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.	From the date of signing consent on the Main study until 90 days after the last day of protocol treatment, on average 3.5 years
Overall survival	Overall survival is defined as the time from randomisation to the date of death due to any cause	From randomisation until last patient has completed 2 years in follow up, on average 3.5 years
Overall quality of life	Quality of Life using the EORTC QLQ-C30 (European Organisation for Research on Treatment of Cancer - Quality of Life Questionnaire for cancer patients) instrument. The instrument uses 28 questions about overall quality of life with each question answerable using a scale from 1 (not at all) to 4 (very much). Overall scores can be from a minimum of 28 indicating a better quality of life and higher scores with a maximum of 112 indicating lower overall quality of life. The questionnaire also has two summary questions which asks participants to rank 1) overall health and 2) overall quality of life on scale of from 1, very poor, to 7, excellent.	From randomisation until last patient has completed 2 years in follow up, on average 3.5 years
Fatigue	Fatigue, using the EORTC FA-12 (European Organisation for Research on Treatment of Cancer - Fatigue) instrument. This instrument uses 12 questions for participants about fatigue with each question answerable on a scale of 1 (not at all) to 4 (Very Much) to a maximum score of 48 indicating worse overall self-rated fatigue.	From randomisation until last patient has completed 2 years in follow up, on average 3.5 years
Fear of progression	Fear of progression using the short FOP12 (Fear of Progression) instrument. This instrument uses 12 questions about participant's own Fear of Progression with each question answerable using a scale from "Never" to "very often" with lower scores indicating a better outcome.	From randomisation until last patient has completed 2 years in follow up, on average 3.5 years
Patient reported adverse events	Patient reported adverse events using the patient reported modified PRO-CTCAE instrument	From randomisation until last patient has completed 2 years in follow up, on average 3.5 years
Frequency of health resource utilisation	To compare resource use associated with mGSTP1 directed therapy per treatment group. Will be measured from trial based eCRFs and will include frequency of mGSTP1 testing, use of docetaxel and corticosteroids, pathology tests and imaging. Men participating in the GUIDE study will be consented for access to their Medicare claims data providing information on outpatient use of PBS listed therapies (such as those for metastatic bone disease) and Medicare services (such as outpatient clinician services)	From time of consent until End of Study, on average 3.5 years
Overall cost associated with treatment	To compare costs associated with treatment per treatment group. Will be reported by type of health care used and the total cost of health care used over the period of the trial and follow-up. Market prices will be applied to items of resource use to estimate costs.	From time of consent until End of Study, on average 3.5 years

Collaborators and Investigators

• Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
• Collaborators: Peter MacCallum Cancer Centre, Australia
• Investigators: Principal Investigator: Kate Mahon, Chris OBrien Lifehouse

Publications and helpful links

Helpful Links

• ANZUP website

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): June 30, 2026

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: June 2, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: ANZUP 1903

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