PET/CT and WB MRI for Staging and Response in CRPC Patients Receiving Enzalutamide

NCT02814968 | Completed Phase 2

• 1 other identifier: EudraCT Number 2014-001161-27
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to assess the clinical utility of 18F-fluoro-deoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) and Whole Body Magnetic Resonance Imaging (MRI) versus conventional bone scan and prostate-specific antigen (PSA) measurements in response prediction to treatment with Enzalutamide in castration-resistant prostate cancer patients. The study will assess how these 2 imaging modalities perform compared to traditional serial PSA measurements and bone scan in assessing metastatic tumour load, progressive disease and response to treatment with Enzalutamide in castration-resistant prostate cancer patients. In addition measurements of serially collected circulating tumour cell (CTC) samples, cell-free tumour DNA and RNA will be performed in order to evaluate their predictive value in terms of response measurement.

Conditions

Prostate Cancer Metastatic

Keywords

Castration-resistant prostate cancer; Enzalutamide; Imaging; PET/CT; Whole body MRI; Circulating tumour cells; Cell-free tumour DNA

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) at 6 months

  Defined as the time from the date of randomization to the date of radiological progression or death (patients will be followed beyond the fixed time point of 12 months for continued response cq recurrence, but 12 month is the last fixed primary endpoint assessment). Radiological progression is defined by any of the following criteria: * Soft tissue lesions: Progressive disease on 18F-FDG PET/CT or MRI by RECIST 1.1. Bone or bone marrow lesions: Progressive disease on PET/CT or MRI as evidenced by new lesions or an increase in size of 25% of the sum of target lesions. * Conversion of the 18F-FDG PET signal of the metastases at 2 weeks, 2 or 6 months compared to baseline PET which by comparing it to PFS at 6 and 12 months may be an indicator or drug response. Radiological PFS at 6 months will be compared to a) PET signal conversion and to b) PSA measurements, and changes in number of lesions on the bone scan (conventional work up).

  6 months

• Progression-Free Survival (PFS) at 12 months

  Defined as the time from the date of randomization to the date of radiological progression or death (patients will be followed beyond the fixed time point of 12 months for continued response cq recurrence, but 12 month is the last fixed primary endpoint assessment). Radiological progression is defined by any of the following criteria: * Soft tissue lesions: Progressive disease on 18F-FDG PET/CT or MRI by RECIST 1.1. Bone or bone marrow lesions: Progressive disease on PET/CT or MRI as evidenced by new lesions or an increase in size of 25% of the sum of target lesions. * Conversion of the 18F-FDG PET signal of the metastases at 2 weeks, 2 or 6 months compared to baseline PET which by comparing it to PFS at 6 and 12 months may be an indicator or drug response. Radiological PFS at 12 months will be compared to a) PET signal conversion and to b) PSA measurements, and changes in number of lesions on the bone scan (conventional work up).

  12 months

Secondary Outcomes (19)

• Biochemical (PSA) response defined as prostate-specific antigen (PSA) nadir.

  12 months

• PSA progression. PSA kinetics measured by PSA doubling time (regular PSA measurements).

  12 months

• Progression of bone lesions detected with bone scan according to Prostate Cancer Working Group 2 (PCWG2) criteria.

  6 and 12 months

• Radiologically confirmed spinal cord compression or pathological fracture due to malignant progression.

  6 and 12 months

• Occurrence of Symptomatic Skeletal Events (SSE) evaluated by combination of clinical and radiological assessments

  12 months

Study Arms (1)

Single arm

EXPERIMENTAL

Subjects will receive 1 dd 160 mg Enzalutamide orally continuously until progressive disease occurs. Serial PSA measurements, PET/CT scans, Whole Body MRI, bone scans will be performed to assess metastatic tumour load, progressive disease and response to treatment.

Drug: Enzalutamide; Device: 18-FDG PET/CT; Device: Whole body MRI; Device: Bone scan

Interventions

Enzalutamide DRUG

Also known as: Xtandi

Single arm

18-FDG PET/CT DEVICE

Single arm

Whole body MRI DEVICE

Single arm

Bone scan DEVICE

Single arm

Eligibility Criteria

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

You may qualify if:

• Male aged 18 years or older;
• Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
• Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy;
• Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA of at least \> 5 ng/mL but preferably \>10 ng/mL;
• Progressive disease as defined by rising PSA levels plus by evidence of progressive and measurable soft tissue or bone disease by 18F-FDG PET/CT, Whole Body MRI or both;
• Castrate serum levels of testosterone \< 50 ng/dL or \< 1.7 nmol/L;
• Anti-androgen withdrawal for at least 6 weeks for bicalutamide, nilutamide or flutamide for at least 6 weeks;
• No prior treatment with cytotoxic chemotherapy;
• Eastern Cooperative Oncology Group (ECOG) score 0-2;
• A life expectancy of at least 12 months;
• Written informed consent.

You may not qualify if:

• Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrolment;
• Known or suspected brain metastasis or active leptomeningeal disease;
• History of another malignancy within the previous 5 years other than curatively treated non melanomatous skin cancer;
• Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal at the Screening visit;
• Creatinine \> 177 µmol/L (2 mg/dL) at the Screening visit;
• Hemoglobin \<6 mmol/L, White blood cells \< 4.0 x10\^9/L, platelets \< 100 x 10\^9/L;
• History of seizure or any condition that may predispose to seizure. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrolment (Day 1 visit);
• Contra-indication for MRI (e.g. pacemaker).

Sponsors & Collaborators

• The European Uro-Oncology Group: lead
• Centre for Human Drug Research, Netherlands: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Related Links

• The European Uro-Oncology Group

MeSH Terms

Interventions

enzalutamide

Study Officials

• Susanne Osanto, MD PhD

  The European Uro-Oncology Group (EUOG)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2016
• First Posted: June 28, 2016
• Study Start: February 1, 2015
• Primary Completion: June 1, 2020
• Study Completion: December 1, 2020
• Last Updated: April 14, 2022

Record last verified: 2021-02

Locations

NL (1)