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

Castration Resistant Prostatic Cancer Clinical Trial

— GUIDE  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04918810
• Other study ID #: ANZUP 1903
• Status: Recruiting
• Phase: Phase 2
• Start date: November 11, 2021
• Est. completion date: June 30, 2026

Study information

• Verified date: March 2023
• Source: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
• Contact: Ronan Burder
• Phone: 03 8559 5088
• Email: ronan.burder[@]petermac.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Castration Resistant Prostatic Cancer
• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant

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.
• 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)

Locations

Country	Name	City	State
Australia	Border Medical Oncology Research Unit / The Border Cancer Hospital	Albury	New South Wales
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	St Vincent's Hospital	Darlinghurst	New South Wales
Australia	Dubbo Base Hospital	Dubbo	New South Wales
Australia	Frankston Hospital-Peninsula Health	Frankston	Victoria
Australia	Goulburn Valley Health	Shepparton	Victoria
Australia	Concord Repatriation General Hospital	Sydney	New South Wales
Australia	LaTrobe Regional Hospital	Traralgon	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
Australian and New Zealand Urogenital and Prostate Cancer Trials Group	Peter MacCallum Cancer Centre, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   ANZUP website