Utilising CTC Counts to Optimize Systemic Therapy of Metastatic Prostate Cancer

NCT03327662 | Terminated Phase 3 DMC

• 1 other identifier: ICR-CTSU/2015/10054
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Adenocarcinoma of the Prostate

Keywords

Cabazitaxel; Docetaxel; Circulating Tumour Cells

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  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

  2 years

Secondary Outcomes (15)

• CTC-guided switch rates

  2 years

• CTC effects on chemotherapy

  2 years

• Toxicity burden assessment

  2 years

• Brief Pain Inventory

  2 years

• The Functional Assessment of Cancer Therapy-Prostate (FACT-P)

  2 years

Other Outcomes (2)

• Patient perception and preferences on therapeutic switch decisions.

  2 years

• Post-trial treatment options

  2 years

Study Arms (2)

Interventional

EXPERIMENTAL

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

Control

NO INTERVENTION

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.

Interventions

Active CTC Assessment OTHER

CTC Counts used to guide treatment switch

Interventional

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Age ≥18 years
• o Tumour tissue blocks will be requested for processing. Sections will be cut with the blocks then returned to the referring hospital. If the block is not available, at least ten tumour tissue sections (formalin-fixed paraffin-embedded) at 5 microns each will be requested.
• Systemic chemotherapy indicated for disease progression, defined as:
• o Bone Scan Progression: Two or more new documented bone lesions over previous 6 months.
• AND/OR
• o Increasing serum PSA level: Two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart are required. If the third PSA value is less than the second, an additional fourth test to confirm the rising PSA is required.
• Baseline laboratory values as stated below:
• Creatinine ≤1.5 x upper limit of normal (ULN)
• Bilirubin ≤1.0 x ULN
• SGOT (AST) and SGPT (ALT) ≤2.5x ULN
• Castrate serum testosterone level (\<50 ng/dL-or-\<1.7 nmol/L)
• ANC ≥1.5 x 109cells/L
• Platelet count ≥100 x 109/L
• PSA ≥ 5ng/mL

You may not qualify if:

• Received any prior cytotoxic chemotherapy as treatment for castration-resistant prostate cancer. Patients that have received chemotherapy for hormone-sensitive metastatic prostate cancer will be allowed onto the trial, if the patient merits retreatment with docetaxel and at least 12 months has elapsed since the patient has completed that previous docetaxel therapy.
• Received any cycling, intermittent or continuous hormonal treatment 28 days prior to randomisation with the exception of the continuous LHRH analogues.
• History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated. Brain imaging for asymptomatic patients is not required.
• Current symptomatic cord compression requiring surgery or radiation therapy. (Once the patient is successfully treated the patient will be considered eligible for the study).
• Active second malignancy (except non-melanoma skin or superficial bladder cancer) defined as requiring anticancer therapy or within the previous two years.
• Serious medical conditions such as heart failure, myocardial infarction, pulmonary thromboembolism within 12 months; stroke or treatment of a major active infection within 3 months of randomisation, as well as any significant medical illness that in the opinion of the Investigator would preclude protocol therapy.
• Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.
• Hypersensitivity to the active substance, to any of its excipients (including polysorbate 80) or to other taxanes.
• Concomitant vaccination with yellow fever vaccine
• Concomitant use of medicinal products that are strong CYP3A inducers

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Prostate Cancer UK: collaborator
• University of Twente: collaborator
• Sanofi: collaborator
• Janssen, LP: collaborator
• Menarini Group: collaborator

Study Sites (4)

The Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Velindre Cancer Centre

Cardiff, United Kingdom

Location

Western General Hospital

Edinburgh, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

Study Officials

• Johann De Bono, MBChB FRCP MSc PhD

  Institute of Cancer Research, United Kingdom

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: October 31, 2017
• Study Start: January 11, 2017
• Primary Completion: November 1, 2019
• Study Completion: April 1, 2020
• Last Updated: January 6, 2021

Record last verified: 2021-01

Locations

GB (4)