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

• ClinicalTrials.gov Identifier: NCT04918810
• Recruitment Status: Recruiting
• First Posted: June 9, 2021
• Last Update Posted: March 29, 2023
• Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
• Collaborator: Peter MacCallum Cancer Centre, Australia
• Information provided by (Responsible Party): Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Tracking Information

• First Submitted Date: May 26, 2021
• First Posted Date: June 9, 2021
• Last Update Posted Date: March 29, 2023
• Actual Study Start Date: November 11, 2021
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 2, 2021)

Radiographic progression free survival (rPFS) [ Time Frame: From randomisation until last patient has completed 2 years in follow up, on average 3.5 years ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 2, 2021)

• Time on treatment holidays [ Time Frame: From randomisation until last patient has completed 2 years in follow up, on average 3.5 years ]
  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
• Overall treatment safety [ Time Frame: 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 ]
  Incidence and severity of adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.
• Overall survival [ Time Frame: From randomisation until last patient has completed 2 years in follow up, on average 3.5 years ]
  Overall survival is defined as the time from randomisation to the date of death due to any cause
• Overall quality of life [ Time Frame: From randomisation until last patient has completed 2 years in follow up, on average 3.5 years ]
  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.
• Fatigue [ Time Frame: From randomisation until last patient has completed 2 years in follow up, on average 3.5 years ]
  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.
• Fear of progression [ Time Frame: From randomisation until last patient has completed 2 years in follow up, on average 3.5 years ]
  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.
• Patient reported adverse events [ Time Frame: From randomisation until last patient has completed 2 years in follow up, on average 3.5 years ]
  Patient reported adverse events using the patient reported modified PRO-CTCAE instrument
• Frequency of health resource utilisation [ Time Frame: From time of consent until End of Study, on average 3.5 years ]
  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)
• Overall cost associated with treatment [ Time Frame: From time of consent until End of Study, on average 3.5 years ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Biomarker-driven Intermittent Docetaxel Versus Standard-of-care (SOC) Docetaxel in Metastatic Castration-resistant Prostate Cancer
• Official Title: 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)

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Parallel Assignment randomised non-comparative

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Castration Resistant Prostatic Cancer

Intervention

• 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.
• 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)

Study Arms

• Experimental: Arm 1: Intermittent docetaxel treatment
  suspend docetaxel prior to cycle 4, recommencement based on mGSTP1 monitoring
  Intervention: Drug: Docetaxel intermittent
• Active Comparator: Arm 2: Standard of Care docetaxel treatment
  Docetaxel administered as per Standard of Care: as per clinician recommendation
  Intervention: Drug: Docetaxel standard of care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 2, 2021): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2026
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ronan Burder; 03 8559 5088; ronan.burder@petermac.org

Contact: Margaret McJannett; 02 9562 5033; margaret@anzup.org.au

• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT04918810
• Other Study ID Numbers: ANZUP 1903
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
• Original Responsible Party: Same as current
• Current Study Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
• Original Study Sponsor: Same as current
• Collaborators: Peter MacCallum Cancer Centre, Australia

Investigators

• Principal Investigator: Kate Mahon; Chris Obrien Lifehouse

• PRS Account: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
• Verification Date: March 2023