The SONImage Study

Study Overview
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Brief Summary
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SONImage is a multicenter prospective imaging side study, in which a baseline FES-PET is added to conventional work up, in 100 patients with ER+ MBC who will receive endocrine treatment ± CDK 4/6 inhibition within the SONIA study (NCT03425838). SONImage will be executed in two Dutch centers: UMCG and Amsterdam UMC-location VUMC. The aim of the SONImage study is to (1) assess the relationship between FES/FDG-PET heterogeneity patterns at baseline and PFS for first-line endocrine treatment ± CDK 4/6 inhibition in ER+ MBC, and (2) to further improve that by developing a prediction model, within the SONIA study. This molecular imaging based multivariable prediction model may provide a unique measure of benefit of adding CDK 4/6 inhibition to first-line endocrine treatment, allowing patients and providers to weigh individual benefits and (long term) burden for optimized treatment decisions.

Detailed Description
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Estrogen receptor positive (ER+) breast cancer is the most common cancer and the most frequent cause of cancer-related death in women in the Western World. Cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors improve outcome, when added to standard first- and second-line endocrine therapy. However, they also add patient- and financial burden due to (long term) increased toxicity and hospital visits. Therefore, benefits of additional CDK 4/6 inhibitors should be weighed against their burden. Tools to support such treatment decisions by patients and providers are currently lacking. Whole body heterogeneity of ER expression, measured by 16α-[18F]fluoro-17β-estradiol (FES)-PET scan and 18F-fluorodeoxyglucose (FDG)-PET scan was related to time to progression on combined treatment in previous work. Therefore in SONImage a baseline FES-PET is added to conventional work up, in 100 patients with ER+ MBC who will receive first line endocrine treatment ± CDK 4/6 inhibition within the SONIA study. The objectives are 1. to correlate PFS1 (according to SONIA criteria) to baseline FES/FDG-PET heterogeneity; 2. to assess interaction between baseline FES/FDG-PET heterogeneity, treatment allocation, and PFS1 (according to SONIA criteria); 3. to correlate response measurements of individual lesions to baseline FES/FDG heterogeneity and detailed FES/FDG imaging features; 4. to develop a multivariable model to predict individual PFS benefit to first-line AI ± CDK 4/6 inhibition, based on detailed FES/FDG image features and standard clinicopathological information, in n=100 SONIA patients; 5. to validate this prediction model in two independent patient cohorts with baseline FES/FDG-PET scans (Dutch IMPACT-MBC trial; international ET-TRANSCAN trial). This molecular imaging based multivariable prediction model may provide a unique measure of benefit of adding CDK 4/6 inhibition to first-line endocrine treatment, allowing patients and providers to weigh individual benefits and (long term) burden for optimized treatment decisions. Particularly for the approximately 25% of patients with ER+ MBC who have an excellent- or poor outcome despite CDK 4/6 inhibition in the first-line, this could have profound implications, as they may refrain from combined treatment. Ultimately, this could potentially contribute to FES/FDG-PET based treatment decisions in clinical practice, reduction of unnecessary toxicity and costs, while improving patient outcome and QoL.

Official Title
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SONImage Study: Can Molecular Imaging Predict Outcome to First-line Endocrine Treatment ± CDK 4/6 Inhibition in Advanced ER+ Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: FES-PET scan, and possibly one additional visit for an FDG-PET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is eligible and participates in the SONIA trial for ER+ MBC. Able to give written informed consent and to comply with the SONImage protocol. Documentation of histologically confirmed diagnosis of estrogen receptor (ER) expression >10% breast cancer based on local results. The receptor status can be determined on the primary tumor or on a tumor biopsy of a metastatic lesion. Exclusion Criteria: A patient who meets the exclusion criteria of the SONIA trial (see SONIA protocol). Contra-indication for PET imaging. Use of estrogen receptor ligands (i.e. tamoxifen or fulvestrant) ≤ 5 weeks before FES-PET imaging.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imaging<br>One visit to either the UMCG or Amsterdam UMC-location VUMC is required for the FES-PET scan, and possibly one additional visit for an FDG-PET. A FES- or FDG-PET scan plus low dose CT will each induce an extra radiation burden of about 6.1 mSv (210 MBq injected for an average patient of 70 kilogram body weight). | Other: FES-PET scan, and possibly one additional visit for an FDG-PET<br>* One visit to either the UMCG or Amsterdam UMC-location VUMC is required for the FES-PET scan, and possibly one additional visit for an FDG-PET. A FES- or FDG-PET scan plus low dose CT will each induce an extra radiation burden of about 6.1 mSv (210 MBq injected for an average patient of 70 kilogram body weight).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival after first line treatment (PFS1) | Progression-free survival after first line treatment (PFS1) defined as time from randomization until objective disease progression, symptomatic deterioration, or initiation of a new therapeutic agent on first line treatment, death, or progression during a break in initial therapy and without further therapy within one month, whichever occurs first. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient response | Per patient response according to RECIST1.1 | 5 years | 
| Response measurement individual lesion | Change in size (=response measurement) per individual lesion at the largest measurable response measured on CT compared to baseline CT | 5 years | 
| Response measurement target lesions | - Per patient trajectory of change in size of target lesions according to RECIST 1.1, from baseline CT until CT at progression of disease. | 5 years |