Clinical trial NCT04125277: The SONImage Study
Official title: SONImage Study: Can Molecular Imaging Predict Outcome to First-line Endocrine Treatment ± CDK 4/6 Inhibition in Advanced ER+ Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
name: BOOG Study Center
First posted: 2019-10-14
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Patient is eligible and participates in the SONIA trial for ER+ MBC.
2. Able to give written informed consent and to comply with the SONImage protocol.
3. 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:

1. A patient who meets the exclusion criteria of the SONIA trial (see SONIA protocol).
2. Contra-indication for PET imaging.
3. Use of estrogen receptor ligands (i.e. tamoxifen or fulvestrant) ≤ 5 weeks before FES-PET imaging.

Primary outcomes:
measure: Progression-free survival after first line treatment (PFS1)
timeFrame: 5 years
Secondary outcomes:
measure: Patient response
timeFrame: 5 years
measure: Response measurement individual lesion
timeFrame: 5 years
measure: Response measurement target lesions
timeFrame: 5 years
Other outcomes:
measure: Association baseline FES/FDG-PET heterogeneity score with primary endpoint.
timeFrame: 5 years
Locations:
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Amsterdam
country: Netherlands
facility: VU Medical Center
Study officials:
affiliation: The Netherlands Cancer Institute
name: C. P. Schröder, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: