Follicular or poorly differentiated cancer refractory to radio iodine MedDRA version: 19.1 Level: PT Classification code 10066474 Term: Thyroid cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: BKM120
Pharmaceutical Form: Capsule, soft
Other descriptive name: BKM120 HYDROCHLORIDE SALT
Sponsors
HOSPICES CIVILS DE LYON
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1- Histologically confirmed differentiated follicular or poorly differentiated thyroid cancer 2- Patients refractory to radio iodine: i.e.; absence of radioiodine uptake in at least one target lesion on a post-therapeutic whole body scan, presence of a target lesion after a cumulative radio-iodine activity of at least 600 mCi, patients with radio-iodine uptake who have progression of the disease within 12 months after radioactive iodine (RAI) treatment 3- Metastatic or locally invasive disease 4- Patients must have at least one site of measurable disease per RECIST (version 1.1.) 5- Documented progression as per RECIST (version 1.1.) based on 2 comparative imagings performed within the last 12 months (+20%) 6- Patients may have received two previous treatment with tyrosine kinase inhibitors but must be off treatment within at least 4 weeks 7- Patient has signed the informed consent before any trial related activities and according to local guidelines 8- Patient (male or female) is = 18 years at the day of consenting to the study 9- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status = 2 which the investigator believes is stable at the time of screening 10- Patient has adequate bone marrow and organ function as defined by the following laboratory values: • Absolute Neutrophil Count (ANC) = 1.0 x 109/L • Platelets = 100 x 109/L • Hemoglobin = 9.0 g/dL • INR = 1,5 • Potassium, calcium, (corrected for serum albumin) and magnesium within normal limits (WNL) for the institution • Serum Creatinine = 1.5 x ULN • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or = 3.0 x ULN if liver metastases are present) • Total Serum bilirubin within normal range (or = 1.5 x ULN if liver metastases are present; or total bilirubin = 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert’s Syndrome which is defined as presence of several episodes of unconjugated hyperbilirubinemia with normal results from CBC count (including normal reticulocyte count and blood smear), normal liver function test results, and absence of other contributing disease processes at the time of diagnosis (see APPENDIX 1) • Fasting plasma glucose (FPG) = 120 mg/dL or = 6.7 mmol/L • HbA1c = 8 % 11- Patient has no legal protection measure 12- Patient has a health coverage (affiliation to social security system or similar) 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1- Other histological subtypes of thyroid tumors: papillary, anaplastic, medullary, lymphoma or sarcoma 2- Patient has received previous treatment with PI3K and/or mTOR inhibitors or AKT inhibitors, 3- Patient has symptomatic central nervous system (CNS) metastases. 4-Patient has a concurrent malignancy or malignancy within 3 years of study enrollment, (with the exception of adequately treated, basal or squamous cell carcinoma or non-melanomatous skin cancer) 5- Patient has a score = 12 on the PHQ-9 questionnaire 6- Patient selects a response of “1, 2 or 3” to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation 7- Patient has a GAD-7 mood scale score = 15 8- Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others) 9- Patient is concurrently using other approved or investigational antineoplastic agent 10- Patient who received wide field radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia, bone marrow and organ functions) 11- Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects of the surgery 12- Patient has active cardiac disease or a history of cardiac dysfunction 13- Patient has a Left Ventricular Ejection Fraction (LVEF) 5 days) with corticosteroids or another immunosuppressive agent, as chronic administration of corticosteroids (> 5 days) can induce CYP3A4 18- Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment contraindicate patient participation in the clinical study (e.g.,chronic pancreatitis, chronic active hepatitis, etc.) 19- Patient has a history of non-compliance to medical regimen or inability to grant consent 20- Patient is currently receiving treatment with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to entry in the treatment phase is allowed. 21- Patient has a known history of HIV (testing not mandatory) infection 22- Pregnant or nursing (lactating) woman where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta hCG laboratory test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to determine efficacy of BKM120 as measured by the progression free survival (PFS rate) at 6 months in patients with progressive, metastatic, refractory, follicular or poorly differentiated thyroid cancers. ;Secondary Objective: • to evaluate the efficacy of BKM120 according to: o The PFS rate at 12 months o The objective tumor response rate (Complete Response + Partial Response according to RECIST (version 1.1.)) after 6 months of treatment o The overall survival (defined as the time from start of study treatment to the date of death due to any cause) at 6 months. • to assess the safety and tolerance of BKM120 ;Primary end point(s): The primary criterion of the study will be progression-free survival (PFS) at 6 months after the onset of the treatment as determined by the radiologist of centers. The progression-free survival is defined as a lack of objective tumor progression and death. Tumor progression is documented by the CT or MRI scans.;Timepoint(s) of evaluation of this end point: 6 months after the onset of the treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS at 12 months - Objective tumor response (CR and PR) after 6 months of treatment according to RECIST criteria (version 1.1.) and validated by a central review committee. - Overall survival (defined as the time from start of study treatment to the date of death due to any cause) at 6 months. - The safety and tolerance of BKM120 at 24 months. - Thyroglobulin determination and relation with tumors changes. - The genetic tumoral alterations including alterations in genes known to be involved in thyroid tumorigenesis (PIK3CA, BRAF, N-RAS) and the predictive value of the tumor molecular profile on the therapeutic effect of the drug. ;Timepoint(s) of evaluation of this end point: 6,12 and 24 months | — |
Countries
France
Contacts
Public ContactZUBLENA
HOSPICES CIVILS DE LYON
Outcome results
None listed