Utilising CTC Counts to Optimize Systemic Therapy of Metastatic Prostate Cancer (CTC-STOP)
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|ClinicalTrials.gov Identifier: NCT03327662|
Recruitment Status : Terminated (Underrecruitment)
First Posted : October 31, 2017
Last Update Posted : January 6, 2021
CTC-STOP is a multicentre prospective randomised controlled phase III trial for metastatic castration-resistant prostate cancer patients.
This study will determine if serial CTC counts can be used as early markers of progression to direct early discontinuation of docetaxel chemotherapy in patients with mCRPC without adversely impacting overall survival, when compared with standard approaches to guide treatment switch decisions.
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma of the Prostate||Other: Active CTC Assessment||Phase 3|
Patients with metastatic castration-resistant prostate cancer will be randomised 1:1 to either control group (standard of care) or intervention group (CTC-guided treatment). All patients will commence first line chemotherapy with docetaxel three-weekly and will receive a minimum of 3 cycles of treatment before any recommendation to discontinue first-line docetaxel.
- Control Group (standard of care): patients will receive first line docetaxel until disease progression according to treating clinician or completion of 10 cycles. Patients and treating clinicians will not be disclosed to the results of CTC determinations.
- Intervention Group (CTC guided treatment): patients will receive first line docetaxel until progression by CTC, and/or disease progression according to treating clinician or completion of 10 cycles. CTC results will be available to the treating clinician to guide decision-making. A progressing CTC count on Day 1 will require confirmation with a second CTC count performed on Day 15 (-/+ 5 days) of that cycle. If a patient is found to have two successive CTC determinations showing progression by CTCs, the clinician will receive a recommendation to discontinue docetaxel on the following cycle.
The reasons of the treating clinician to discontinue docetaxel will be reported in both groups. Patients who discontinue first line docetaxel according to the criteria for each group will be switched to second line chemotherapy with cabazitaxel. After progression on cabazitaxel or completion of 10 cycles, patients will be followed up for survival every three months until end of study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Patients with CTC count >5 CTC/7.5 mL at screening will be randomised 1:1 to either the control group (standard of care) or intervention group (CTC guided treatment). All patients will commence first line chemotherapy with docetaxel 75mg/m2 three-weekly and will receive a minimum of 3 cycles of treatment before any recommendation to discontinue first-line docetaxel.|
|Masking:||None (Open Label)|
|Official Title:||Utilising Circulating Tumour Cell (CTC) Counts to Optimize Systemic Therapy of Metastatic Prostate Cancer: CTC-STOP Trial|
|Actual Study Start Date :||January 11, 2017|
|Actual Primary Completion Date :||November 2019|
|Actual Study Completion Date :||April 2020|
Active CTC assessment: Patients will receive first line docetaxel until progression by CTC, and/or disease progression according to treating clinician or completion of 10 cycles. CTC results will be available to the treating clinician to guide decision-making. A progressing CTC count on Day 1 will require confirmation with a second CTC count performed on Day 15 (-/+ 5 days) of that cycle. If a patient is found to have two successive CTC determinations showing progression by CTCs, the clinician will receive a recommendation to discontinue docetaxel on the following cycle.
Other: Active CTC Assessment
CTC Counts used to guide treatment switch
No Intervention: Control
Patients will receive first line docetaxel until disease progression according to treating clinician or completion of 10 cycles. Patients and treating clinicians will not be disclosed to the results of CTC determinations.
- Overall Survival [ Time Frame: 2 years ]
OS is defined as the time from the date of randomisation to the date of death (due to any cause). Patients alive at end of follow-up will be censored at the last documented date of follow-up.
An initial non-inferiority analysis will be conducted followed by a superiority analysis if non-inferiority is demonstrated
- CTC-guided switch rates [ Time Frame: 2 years ]Proportion of patients in the intervention group that undergo a chemotherapy switch from docetaxel to cabazitaxel guided by CTC results that fulfil the pre-specified criteria for progression.
- CTC effects on chemotherapy [ Time Frame: 2 years ]To determine if the study of serial CTC counts will decrease the administration of cytotoxic chemotherapy, number of cycles of chemotherapy in both groups will be reported.
- Toxicity burden assessment [ Time Frame: 2 years ]Incidence of treatment-emergent adverse events (safety and tolerability) will be assessed throughout the treatment period using the NCI CTCAE v4.0 and summarised in tabular format. Reported toxicities will be coded using MedDRA (current version)
- Brief Pain Inventory [ Time Frame: 2 years ]validated questionnaire that assesses pain severity (four items) and pain interference (11 items). Pain severity is measured through patients' rating of their level of current pain, average pain, least pain in the last 24 hours and worst pain in the last 24 hours, using an 11-point numerical rating scale (NRS) ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The 'Worst Pain' and 'Average Pain' items of the BPI-SF are often used in clinical trials to singly represent pain severity.
- The Functional Assessment of Cancer Therapy-Prostate (FACT-P) [ Time Frame: 2 years ]FACT-P is a relevant, worldwide Patient reported outcome measure tool used for assessing the health-related quality of life in men with prostate cancer. The FACT-P will be used in this study as part of a wider Quality of Life analysis to compare both arms.
- EuroQoL Five Dimensions (EQ-5D) [ Time Frame: 2 years ]EQ-5D is a self reported questionnaire measuring generic health status. EQ-5D will be used in this study as part of a wider Quality of Life analysis to compare both arms.
- Progression Free Survival [ Time Frame: 2 years ]PFS will be measured from the date of randomisation to the date of death (due to any cause) or disease progression (As per PCWG2 criteria), whichever occurs first. Patients alive and progression-free at the last documented date of follow-up will be censored at that date.
- Radiographic Progression Free Survival (rPFS) [ Time Frame: 2 years ]
rPFS will be measured from randomisation to the occurrence of one of the following:
- Development of new nodal / soft tissue (inclusive of measurable soft tissue associated with lytic bone -metastases) lesions by CT as defined in RECIST 1.1 criteria, and/or
- Progression of bone disease by PCWG2 bone scan criteria and/or,
- Death of any cause
In case of progression by bone scan, the date of progression will be considered as the date of the first bone scan showing new lesions.
- Time to First Symptomatic Skeletal Related Event (SSRE) [ Time Frame: 2 years ]
The time to the first SSRE will be defined will be measured from the date of randomisation to the date of any of the following:
- First use of external-beam radiation therapy to relieve skeletal symptoms
- New symptomatic pathologic vertebral or non-vertebral bone fractures
- Spinal cord compression
- Tumour-related orthopaedic surgical intervention
Patients alive and free of SSRE at the last documented date of follow-up will be censored at that date.
- Time to CTC Progression [ Time Frame: 2 years ]
CTC progression will be based on serial CTC levels collected during the study. Time to CTC Progression will be defined as the time from randomisation to the time of first blood test showing progression by CTCs, defined by:
- Failure to achieve a 30% decline from Screening CTC counts (baseline) AND a failure to achieve a conversion from unfavourable (≥ 5 cells/7.5 mL) to favourable (< 5 cells/7.5 mL) count; or
- Conversion from favourable to unfavourable CTC counts after a previous CTC response; or
- A 30% increase in CTC count from nadir after a previous CTC response and an unfavourable CTC count (i.e. CTC ≥ 5 cells/7.5 mL).
An additional CTC count will be required to confirm progression. If confirmed, the date of the first CTC count meeting criteria for progression will be used as progression date.
- Circulating Tumour Cells (CTC) counts [ Time Frame: 2 years ]
Serial CTC levels collected during the study will be compared to evaluate the % CTC change from Screening (baseline). Change at any time point will be classified into response CTC (decline >30%), stable CTC (change between -30% and 30%) and progressive CTC (increase >30%).
The endpoint of interest for this study is the proportion of patients with a stable CTC count by 12-weeks (or earlier if treatment discontinued).
- Prostate Specific Antigen (PSA) Counts [ Time Frame: 2 years ]PSA values will be measured at regular timepoints in the study. At each time point where PSA is measured, % change from baseline PSA value will be measured, maximum PSA decline at any time and decline after 12 weeks on 1st and 2nd line chemotherapy will be reported.
- Rate of CTC Response [ Time Frame: 2 years ]
CTC response is defined by:
- A conversion from unfavourable (>= 5 CTC/7.5 mL) to favourable (< 5 CTC/7.5 mL) CTC counts OR
- A 30% or more decrease in CTC counts from screening (baseline).
- Rate of Pain response [ Time Frame: 2 years ]
Pain response will be evaluated only in patients with a median BPI score of ≥2 and will be defined as a reduction of 2 points or more from baseline median BPI score without an increase in analgesic score maintained for 3 or more weeks.
Pain Progression Pain progression will be defined as an increase of at least two-points in the worst pain score over the mean baseline score (as defined by the baseline BPI), maintained for at least two consecutive measurements approximately 3-weeks apart.
- Health Economic assessment [ Time Frame: 2 years ]A decision analytic model will be developed, modelling the CTC guided and comparator interventions. The model will analyse the most cost-effective strategy for the management of patients with progressive disease.
- Patient perception and preferences on therapeutic switch decisions. [ Time Frame: 2 years ]Patient perception and preferences on therapeutic switch decisions will be assessed by the Treatment Switch Questionnaire, purposely designed by the study team.
- Post-trial treatment options [ Time Frame: 2 years ]Post-trial treatment will be collected for all patients during follow-up.
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): NCT03327662
|The Royal Marsden Hospital|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|Velindre Cancer Centre|
|Cardiff, United Kingdom|
|Western General Hospital|
|Edinburgh, United Kingdom|
|University College London Hospital|
|London, United Kingdom|
|Principal Investigator:||Johann De Bono, MBChB FRCP MSc PhD||Institute of Cancer Research, United Kingdom|