Imaging Staging and Response Prediction in Metastatic Hormono-Sensitive Prostate Cancer Patients Receiving Enzalutamide

Sponsor

The European Uro-Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT02815033

Collaborator

Centre for Human Drug Research, Netherlands (Other)

Enrollment

Location

Arm

65.1

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the study is to assess the clinical utility of 11C or 18F-Choline Positron Emission Tomography (PET)/Computed Tomography (CT) scan, Whole Body Magnetic Resonance Imaging (MRI) versus conventional bone scan and prostate-specific antigen (PSA) measurements in response prediction to treatment with Enzalutamide in Hormono-Sensitive Metastatic 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 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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer Metastatic	Drug: Enzalutamide Procedure: 11C or 18F-Choline PET/CT Procedure: Whole body MRI Procedure: Bone scan	Phase 2

Detailed Description

Metastatic prostate cancer patients eligible for 1st line hormonal treatment will undergo treatment with Enzalutamide (XTANDI). Subjects will receive 1dd 160 mg Enzalutamide orally continuously until progressive disease occurs. All subjects will undergo Choline (11C or 18F)-PET/CT scans at baseline, 2 weeks, 2 and 6, 9 and 12 months after starting androgen receptor (AR)-directed treatment. All subjects will undergo Whole Body MRI at baseline, 6, 9 and 12 months. Bone scans will be performed at baseline, 3 months, 6 and 12 months. PSA will be measured at baseline and every 4 weeks thereafter until at 12 months. CTC counts and characteristics will be measured at baseline and during Enzalutamide treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

66 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Exploratory Phase 2, Open-label, Single-arm, Efficacy and Imaging Study of Oral Enzalutamide (XTANDI) Androgen Receptor (AR)-Directed Therapy in Hormono-Sensitive Patients With Metastatic Prostate Cancer (Hormono-sensitive Patients)

Study Start Date :

Jul 1, 2015

Actual Primary Completion Date :

Jun 1, 2020

Actual Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Single arm Experimental: Single arm 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 Other Names: Xtandi Procedure: 11C or 18F-Choline PET/CT Procedure: Whole body MRI Procedure: Bone scan

Arm

Intervention/Treatment

Other: Single arm

Experimental: Single arm 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

Other Names:

Xtandi

Procedure: 11C or 18F-Choline PET/CT

Procedure: Whole body MRI

Procedure: Bone scan

Outcome Measures

Primary Outcome Measures

Progression-Free Survival (PFS) at 6 and 12 months. [6 and 12 months]
Radiological progression is defined by any of the following criteria: Soft tissue lesions: Progressive disease on Choline (11C or 18F) PET/CT or Whole Body 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 Choline (11C or 18F) 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 and 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).

Secondary Outcome Measures

Biochemical response defined as prostate-specific antigen (PSA) nadir [12 months]
Assessment of nadir PSA
PSA progression. PSA kinetics measured by PSA doubling time (regular PSA measurements) [12 months]
PSA doubling time
Progression of bone lesions detected with bone scan according to Prostate Cancer Working Group 2 (PCWG2) criteria [6 and 12 months]
Bone lesions progression
Radiologically confirmed spinal cord compression or pathological fracture due to malignant progression [6 and 12 months]
Assessment of spinal cord compression or pathological fracture
Occurrence of Symptomatic Skeletal Events (SSE) evaluated by combination of clinical and radiological assessments [12 months]
SSE is defined as external beam radiation therapy to relieve skeletal pain, occurrence of a new symptomatic pathologic bone fracture, spinal cord compression, tumour-related orthopedic surgical intervention or change of anti-neoplastic therapy to treat bone pain
Circulating tumour cell (CTC) measurements and comparison with radiological PFS at 6 and 12 months [6 and 12 months]
Assessment of CTC
Percent change from baseline in serum concentration of circulating testosterone (T) [12 months]
Changes in testosterone from baseline
Percent change from baseline in serum concentration of dihydrotestosterone (DHT) [12 months]
Changes in dihydrotestosterone from baseline
Percent change from baseline in serum concentration of sex hormone binding globulin (SHBG) [12 months]
Changes in sex hormone binding globulin
Percent change from baseline in serum concentration of androstenedione (A) [12 months]
Changes in androstenedione from baseline
Number of participants with changes in biomarkers of bone turnover correlated to PSA [12 months]
Changes in biomarkers of bone turnover correlated to PSA
Number of participants with adverse events (AEs) and serious adverse events (SAEs) leading to treatment discontinuation [6 and 12 months]
Assessment of AE and SAEs
Time to symptomatic progression (including death due to prostate cancer) [12 months]
Time to progression
Time to first radiological or symptomatic progression [6 and 12 months]
Time to first radiological or symptomatic progression
Time to initiation of salvage systemic therapy, including chemotherapy, or palliative radiation [12 months]
Time to chemotherapy or palliative radiation
Quality of life measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire [6 and 12 months]
Quality of Life measurement using questionnaires
Quality of life measured by the EuroQol 5-Dimension QoL Instrument (EQ-5D) [6 and 12 months]
Quality of life measurement using questionnaire
Changes in Sexual Function (IIEF) [6 and 12 months]
Changes in Sexual Function from baseline
Changes in Karnofsky score [6 and 12 months]
Changes in Karnofsky score from baseline
Changes in visual analogue scale (VAS) for tumour-related pain [6 and 12 months]
Changes in pain from baseline
Changes in bone mineral density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA) scan [6 and 12 months]
Changes in bone mineral density from baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Male aged 18 years or older;
Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA of at least > 2 ng/mL but preferably >20 ng/mL;
Progressive disease defined by rising PSA levels plus by evidence of progressive and measurable soft tissue or bone disease by 11C or 18F-Choline PET/CT, Whole Body MRI or both;
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;

Exclusion Criteria:

Treatment with androgen deprivation therapy with a gonadotropin-releasing hormone analogue, luteinizing hormone-releasing hormone antagonist, or bilateral orchiectomy within 6 months of enrolment (Day1 visit);
Treatment with anti-androgens such as bicalutamide, nilutamide or flutamide within 6 weeks of enrolment (Day 1 visit);
Treatment with 5-α reductase inhibitors (finasteride, dutasteride), estrogens, cyproterone acetate within 4 weeks of enrolment (Day 1 visit);
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 x 10^{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).