A multicenter phase II pilot open label study to evaluate the efficacy and safety of BKM120 in the treatment of patients with advanced or metastatic differentiated thyroid cancers
- Conditions
- Follicular or poorly differentiated cancer refractory to radio iodineMedDRA version: 19.1Level: PTClassification code 10066474Term: Thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-003814-15-FR
- Lead Sponsor
- HOSPICES CIVILS DE LYO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
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
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) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
14- Patient has any of the following cardiac conduction abnormalities:
15- Patient is currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to randomization.
16- Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
17-Patient is currently receiving increasing or chronic treatment (> 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method