Open-label, phase II, basket trial. This trial is a screening program for abemaciclib efficacy in multiple platinum-resistant tumour types by using metabolic imaging (PERCIST) and RECIST v1.1 criteria. Based on the rate of FDG-avidity and the absence of deactivation of the Rb gene function in more than 95% of cases, we propose to define 5 tumour types of interest in a preliminary stage: 1. Platinum-refractory esophageal adenocarcinoma (ADC) 2. Platinum-refractory esophageal squamous cell carcinoma (SCC) 3. Platinum-refractory cholangiocarcinoma 4. Platinum-refractory and progressive after immunotherapy urothelial cancer 5. Platinum-refractory endometrial cancer
In various solid tumour types FDG-PET/CT has been shown to identify treatment-refractory diseases with a high negative predictive value (NPV) through a whole-body quantitative assessment of treatment-induced changes in tumour glucose uptake soon after treatment initiation, before any structural changes are observed. Progress in the standardisation of FDG-PET/CT imaging and response analysis now allow its use in multicentric trials opening the possibilities for trials where treatment allocation will be based on early metabolic response. MiMe has been built on the assumption that a medication which does not induce any metabolic changes in a given clinical setting is unlikely to induce a significant benefit and does consequently not deserve further investigation as a single agent in this setting. MiMe, by assessing metabolic response early during the treatment course, will hopefully provide useful information about the drug activity in various cancer types, and about mechanisms of resistance through a potential ambitious translational research program with serial collection of circulating-tumour DNA (ct-DNA).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
85
Subjects will receive 200 mg of abemaciclib orally, two times a day, during cycles of 28 days each. An early FDG-PET/CT will be performed at cycle 1 day 14 to search for any new lesions.
Universitair Ziekenhuis
Antwerp, Belgium
Institut Jules Bordet
Brussels, Belgium
Algemeen Ziekenhuis Groeninge
Kortrijk, Belgium
CHC Saint-Joseph
Liège, Belgium
CHU Ambroise Paré
Mons, Belgium
CHU UCL Namur Sainte-Elisabeth
Namur, Belgium
Centre Oscar Lambret
Lille, France
Institut Paoli-Calmettes
Marseille, France
Centre Henri Becquerel
Rouen, France
Hôpital universitaire de Strasbourg - ICANS
Strasbourg, France
...and 1 more locations
Evaluate the anti-tumour activity of abemaciclib in the five tumour types studied in this trial using FDG-PET/CT during the first cycle of therapy (early FDG- PET/CT).
Therapy success rate defined as: PERCIST 15%-assessed Metabolic Response at early FDG-PET/CT (D12-D16)
Time frame: 2 months
Evaluate the anti-tumour activity of abemaciclib in the five tumour types studied in this trial using RECISTv1.1 after 2 cycles of therapy as a screening tool.
Therapy success rate defined as: RECISTv1.1-assessed Disease Control (DC) after 2 treatment cycles (CR or PR or SD)
Time frame: 2 Months
Evaluate Progression-free survival (PFS define as the time from treatment start until disease progression or death) at 24 weeks from treatment start
RECIST v1.1-based radiological response assessment performed at 24 weeks from the treatment start to determine the PFS
Time frame: 6 months
Evaluate Overall Survival (OS defined as the time from treatment start until death) at 24 weeks from treatment start
RECIST v1.1-based radiological response assessment performed at 24 weeks from the treatment start to determine the OS.
Time frame: 6 months
To evaluate median progression-free survival (PFS)
Progression Free Survival
Time frame: 42 months
Evaluate median overall survival (OS)
Overall Survival
Time frame: 42 months
To evaluate toxicity profile
Toxicity profile according to CTCAE version 4.03
Time frame: 6 months
Evaluate the correlation of early metabolic response using FDG-PET/CT with morphological response to treatment assessed by RECIST
RECIST v1.1-based radiological response assessment performed at 24 weeks from the treatment start to determine the PFS and OS
Time frame: 6 months
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