The SONImage Study
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Imaging 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
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).
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Outcome Measures
Primary Outcome Measures
- Progression-free survival after first line treatment (PFS1) [5 years]
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.
Secondary Outcome Measures
- Patient response [5 years]
Per patient response according to RECIST1.1
- Response measurement individual lesion [5 years]
Change in size (=response measurement) per individual lesion at the largest measurable response measured on CT compared to baseline CT
- Response measurement target lesions [5 years]
- Per patient trajectory of change in size of target lesions according to RECIST 1.1, from baseline CT until CT at progression of disease.
Other Outcome Measures
- Association baseline FES/FDG-PET heterogeneity score with primary endpoint. [5 years]
Cox-regression to estimate HRs for PFS and corresponding 95% CIs between FES/FDG heterogeneity groups, while adjusting for treatment allocation.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patient is eligible and participates in the SONIA trial for ER+ MBC.
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Able to give written informed consent and to comply with the SONImage protocol.
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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:
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A patient who meets the exclusion criteria of the SONIA trial (see SONIA protocol).
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Contra-indication for PET imaging.
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Use of estrogen receptor ligands (i.e. tamoxifen or fulvestrant) ≤ 5 weeks before FES-PET imaging.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | VU Medical Center | Amsterdam | Netherlands | ||
| 2 | University Medical Center Groningen | Groningen | Netherlands | 9713 GZ |
Sponsors and Collaborators
- University Medical Center Groningen
- Dutch Cancer Society
- BOOG Study Center
Investigators
- Principal Investigator: C. P. Schröder, MD, PhD, University Medical Center Groningen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 201900572