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

The European Uro-Oncology Group66 enrolled

Overview

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.

Castration-resistant prostate cancer patients eligible for 2nd 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 18F-FDG PET/CT scans at baseline, 2 weeks, 2 and 6, 9 and 12 months after starting androgen receptor-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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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).

Outcomes

Primary Outcomes

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).

Time frame: 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).

Time frame: 12 months

Secondary Outcomes

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

Response as PSA nadir.

Time frame: 12 months

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

PSA doubling time

Time frame: 12 months

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

Progression of bone lesions

Time frame: 6 and 12 months

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

Radiological assessment of spinal cord compression or pathological fracture

Time frame: 6 and 12 months

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

Assessment of 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

Time frame: 12 months

Number of participants with change in CTC measurements correlated to radiological PFS.

Assessment of radiological PFS

Time frame: 6 and 12 months

Percent change from baseline in serum concentration of circulating testosterone (T).

Change in circulating testosterone

Time frame: 12 months

Percent change from baseline in serum concentration of dihydrotestosterone (DHT).

Change in serum concentration of dihydrotestosterone

Time frame: 12 months

Percent change from baseline in serum concentration of sex hormone binding globulin (SHBG).

Changes of SHBG

Time frame: 12 months

Percent change from baseline in serum concentration of androstenedione (A).

Changes of androstenedione from baseline

Time frame: 12 months

Number of participants with changes in biomarkers of bone turnover correlated to PSA.

Changes in biomarkers

Time frame: 12 months

Number of participants with adverse events (AEs) and serious adverse events (SAEs) leading to treatment discontinuation.

Assessment of AE and SAEs

Time frame: 6 and 12 months

Time to symptomatic progression (including death due to prostate cancer).

Time to progression

Time frame: 12 months

Time to initiation of salvage systemic therapy, including chemotherapy, or palliative radiation.

Time to chemotherapy or palliative radiation.

Time frame: 12 months

Quality of life measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.

Quality of life assessment

Time frame: 6 and 12 months

Quality of life measured by the EuroQol 5-Dimension QoL Instrument (EQ-5D).

Quality of life assessment

Time frame: 6 and 12 months

Changes in Karnofsky score

Time frame: 6 and 12 months

Changes in visual analogue scale (VAS) for tumour-related pain.

Pain changes from baseline (QoL)

Time frame: 6 and 12 months

Changes in bone mineral density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA) scan.

Bone mineral density changes

Time frame: 6 and 12 months

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes