Brief Title
Multiorgan Metabolic Imaging Response Assessment of Abemaciclib
Official Title
Multiorgan Metabolic Imaging Response Assessment of Abemaciclib
Brief Summary
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
Detailed Description
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
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).
Secondary Outcome
Evaluate Progression-free survival (PFS define as the time from treatment start until disease progression or death) at 24 weeks from treatment start
Condition
Esophageal Adenocarcinoma
Intervention
Abemaciclib
Study Arms / Comparison Groups
Abemaciclib
Description: This study contains 2 stages; during the 1st stage, a maximum of 17 patients will be enrolled in each tumour type cohort. After 13 evaluable patients have been enrolled, an interim analysis will be performed. If 3 or more patients are seen to have experienced a treatment success, then the cohort will pass into the 2nd stage in which a maximum of 20 more patients are enrolled. If 2 or less patients are seen to have experienced a treatment success, then that cohort will be closed and will not proceed into the 2nd stage. Subjects will receive 200 mg of abemaciclib orally, twice a day, during cycles of 28 days each. The subject will undergo: A baseline FDG-PET/CT and a baseline CT scan and A blinded early FDG-PET/CT at D14 +/- 2 days of study treatment. A treatment success is defined as a patient who has metabolic response according to PERCIST with a response cut off set at 15% at the early FDG-PET/CT and a morphological disease control after 2 cycles measured by RECIST v1.1.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
85
Start Date
December 19, 2018
Completion Date
October 15, 2021
Primary Completion Date
October 15, 2021
Eligibility 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) and metastatic or non-resectable and refractory to standard platinum regimens
(and progressive after immunotherapy for the urothelial cancer).
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 v 1.1
8. Serum pregnancy test (for subjects of childbearing potential) negative
9. Women of childbearing potential must agree to the use a 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 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 ≥ 10 g/dL
- Absolute neutrophil count ≥ 1500/µL or 1.5x109/L
- Platelets ≥ 100000/µL or 100x109/L
- Leukocytes ≥ 3,000/µL
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 <1.5 institutional ULN)
- AST/ALT/ALP) levels < 3 × institutional upper limit of normal (or ALT and AST <5
times upper limit of normal if liver metastases are present).
14. Adequate renal function as defined below: Cockcroft-Gault creatine clearance >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.4.03). Grade 2
is allowed in case of alopecia and peripheral sensory neuropathy
18. Availability of primary archived tumour tissue block (1 FFPE tumour tissue)
19. Signed Informed Consent form (ICF) obtained prior to any study related procedure
Exclusion Criteria:
1. Subjects meeting one of the following criteria are not eligible for this
studyParticipants who have had chemotherapy, radiotherapy, immunotherapy, or targeted
therapy within 3 weeks prior study enrolment
2. Participants receiving concomitantly any other experimental agents
3. Patients who have received prior therapy with other CDK4/6 inhibitors
4. Subjects with known brain metastasis; unless the metastasis are asymptomatic and have
been stable since at least 2 months prior to treatment start.
5. Patient with 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Laura Polastro, MD, +3225413279, [email protected]
Location Countries
Belgium
Location Countries
Belgium
Administrative Informations
NCT ID
NCT03339843
Organization ID
IJB-MULTI-MIME-A-2017
Responsible Party
Sponsor
Study Sponsor
Jules Bordet Institute
Collaborators
Eli Lilly and Company
Study Sponsor
Laura Polastro, MD, Study Chair, Jules Bordet Institute
Verification Date
November 2018