esophageal ADC, esophageal SCC, Cholangiocarcinoma, urothelial cancer (progressive after immunotherapy), or endometrial cancer MedDRA version: 20.0 Level: LLT Classification code 10055458 Term: Esophageal adenocarcinoma System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10055476 Term: Esophageal squamous cell carcinoma System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10008595 Term: Cholangiocarcinoma NOS System Organ Class:
Conditions
Sponsors
Institut Jules Bordet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years old 2. Female or Male 3. ECOG performance status = 1 4. Life expectancy of greater than 12 weeks 5. Must have histologically confirmed cancer corresponding to the predefined tumour subtypes (esophageal adenocarcinoma, esophageal squamous cell carcinoma, cholangiocarcinoma, urothelial cancer (progressive after immunotherapy), endometrial cancer) that are metastatic or non-resectable and refractory to standard platinum regimens (and progressive after immunotherapy for urothelial cancer if available). 6. Presence of at least one metabolically measurable tumour lesion on FDG-PET/CT, according to PERCIST. If previously irradiated, must have been more than 2 months before the baseline FDG PET/CT. 7. Measurable disease according to RECIST v1.1 8. Negative serum pregnancy test (for subjects of childbearing potential). 9. Women of childbearing potential must agree to the use of 1 highly effective method of contraception prior to study entry, during the course of the study and at least 3 months after the last administration of study treatment. 10. Men with childbearing potential partner must agree to use a condom during the course of this study and for at least 3 months after the last administration of the study treatment. 11. Adequate coagulation: International Normalized Ratio (INR) = 1.5 x ULN unless subject is receiving anticoagulant therapy as long as INR and activated partial thromboplastin time [aPTT] are within therapeutic range of intended use of anticoagulants 12. Adequate bone marrow function as defined below: • Hemoglobin = 10g/dl • Absolute neutrophil count = 1500/µL or 1.5x109/L • Platelets = 100000/µL or 100x109/L • Leukocytes = 3,000/mcL 13. Adequate liver function as defined below: • Serum total bilirubin within 1.5 × normal institutional limits (except for Gilbert syndrome where direct bilirubin should be 50ml/min 15. Completion of all necessary screening procedures 16. Ability to swallow capsules 17. Grade = 1 toxicity due to any previous cancer therapy according to the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE v 5.0). Grade 2 is allowed in case of alopecia and peripheral sensory neuropathy. 18. If primary archived tumour tissue block available, it must be provided. (1 FFPE tumour tissue or 20 unstained slides) 19. Signed Informed Consent form (ICF) obtained prior to any study related procedure Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 185 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Have had chemotherapy, radiotherapy, immunotherapy, or targeted therapy within 3 weeks prior study enrolment 2. Receiving concomitantly any other experimental agents 3. Have received prior therapy with other CDK4/6 inhibitors 4. Known brain metastasis; unless the metastasis are asymptomatic and have been stable since at least 2 months prior to treatment start. 5. Have meningeal carcinomatosis 6. Have had major surgery within 28 days prior to the start of the treatment to allow for post-operative healing of the surgical wound 7. History of allergic reactions attributed to compounds of similar chemical or biologic composition 8. Bleeding diathesis, thromboembolic event, history of cardiovascular ischemic disease or cerebrovascular incident within the last six months 9. Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia 10. Substance abuse, psychiatric illness/social situations, any psychological, familial, sociological, geographical condition, significant medical or surgical condition currently uncontrolled by treatment that would limit compliance with study requirements or interfere with the patient’s ability to understand informed consent and participation in the study 11. Pregnant and/or lactating women 12. Uncontrolled Diabetes 13. Known history of HIV infection, or active hepatitis B or C requiring treatment with anti-viral therapy 14. Have received recent (within 28 days prior the enrolment) yellow fever vaccination 15. Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free and are deemed by the investigator to be at low risk for recurrence of that malignancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the anti-tumour activity of abemaciclib in the five tumour types studied in this trial using the combination of FDG-PET/CT during the first cycle of therapy (early FDG- PET/CT) and RECIST v1.1 after 2 cycles of therapy as a screening tool.;Secondary Objective: In each tumour type population: •To evaluate Progression-free survival (PFS define as the time from treatment start until disease progression or death) and Overall Survival (OS defined as the time from treatment start until death) at 24 weeks from treatment start, •To evaluate median progression-free survival (PFS) and median overall survival (OS) •To evaluate safety/toxicity profile •To evaluate the correlation of early metabolic response using FDG-PET/CT with morphological response to treatment assessed by RECIST ;Primary end point(s): Therapy success rate defined as: •PERCIST 15%-assessed Metabolic Response at early FDG-PET/CT (D12-D16) and •RECIST v1.1-assessed Disease Control (DC) after 2 treatment cycles (CR or PR or SD);Timepoint(s) of evaluation of this end point: end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In each tumour type population: • RECIST v1.1-based radiological response assessment performed at 24 weeks from the treatment start to determine the PFS and OS. • Progression Free Survival • Overall Survival • Safety/Toxicity profile according to CTCAE version 5.0 ;Timepoint(s) of evaluation of this end point: end of the study | — |
Countries
Belgium, France
Contacts
Public ContactCTSU
Institut Jules Bordet
Outcome results
None listed