Patients with metastatic or relapsed head and neck cancer and documented progression or relapse after platin and cetuximab-based chemotherapy (combination or sequential treatment) MedDRA version: 14.1 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: BKM120
Product Code: BKM120
Pharmaceutical Form: Capsule, hard
Current Sponsor code: BKM120
Other descriptive name: PI3K I
Sponsors
Centre Léon Berard
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I1.Adult men and women = 18 years at the day of inform consent signature. I2.Patients with metastatic or relapsed head and neck cancer. I3.Documented progression or relapse after platin and cetuximab-based chemotherapy (combination or sequential treatment). I4.Documented mutational status of PIK3CA before inclusion (molecular pre-screening). I5.Eastern Cooperative Oncology Group (ECOG) performance status = 2 I6.At least one measurable lesion by CT-scan as per RECIST 1.1 . I7.Life expectancy > 12 weeks. I8.Adequate bone marrow, renal and liver function as defined by the following tests (to be carried out 7 days prior to starting 1st treatment cycle): ?Absolute neutrophil count > 1.0 x 109/L, ?Platelet count > 100 x 109/L, ?Haemoglobin value above 9 g/dL, ?INR > 1.5 ?Serum Creatinine = 1.5 ULN ?Glomerular filtration rate calculated using Cockroft-Gault formula > 60ml/min (or MDRD formulae for patients older than 65 years) ?Potassium, calcium, magnesium within normal limits for the institution ?Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: E1.Patient having received previous treatment with PI3K and/or mTOR inhibitors E2.Patient with symptomatic CNS metastases E3.Patient with a concurrent malignancy or has a malignancy within 3 years of study enrollment, (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer) E4.Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist oMedically 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 (immediate risk of doing harm to others) o= CTCAE grade 3 anxiety oor meets the cut-off score of = 12 in the PHQ-9 or a cut-off of = 15 in the GAD-7 mood scale, respectively, oor selects a positive response of ‘1, 2, or 3’ to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9). E5.Patient concurrently using other approved or investigational anti-neoplasic agent E6.Patient who has 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). E7.Patient having had major surgery within 14 days prior to starting study drug or has not recovered from major side effects of the surgery E8.Patient with poorly controlled diabetes mellitus (i.e. HbA1c > 8 %) E9.Patient with active cardiac disease including any of the following: oLeft Ventricular Ejection Fraction (LVEF) 480 (female) or 470 msec (male) on screening ECG (using the QTcF formulae) oAngina pectoris that requires the use of anti-anginal medication oVentricular arrhythmias except for benign premature ventricular contractions oSupraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication oConduction abnormality requiring a pacemaker oValvular disease with documented compromise in cardiac function oSymptomatic pericarditis E10.Patient with a history of cardiac dysfunction including any of the following; oMyocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function oHistory of documented congestive heart failure (New York Heart Association functional classification III-IV) oDocumented cardiomyopathy oOther cardiac arrhythmia not controlled with medication E11.Patient currently receiving treatment with QT prolonging medication known to have a risk to induce Torsades de Pointes (see Appendix 05), and if the treatment cannot be discontinued or switched to a different medication prior to starting study drug E12.Patient with impairment of gastrointestinal (GI) function or GI disease tha
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the activity of BKM120 as measured by the 2-month disease control rate (Complete response + Partial Response + Stable disease according to RECIST 1.1) in adult patients with recurrent or metastatic head and neck cancer progressive under platin and cetuximab-based chemotherapy.; Secondary Objective: o To further assess the activity of BKM120 as measured by progression-free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response, time to progression (TTP) and time to treatment failure (TTF). o To assess the safety and tolerance of BKM120 in this patient population. o To assess the 18F-FDG-PET changes reflecting the inhibition of the tumor metabolic activity. ;Primary end point(s): disease control rate after 2 months of treatments;Timepoint(s) of evaluation of this end point: 2 months of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression-free survival will be measured from the date of treatment start to the date of event defined as the first documented disease progression or death from any cause. Patients with no event at the time of analysis will be censored at their last tumor assessment date. Overall survival will be measured from the date of inclusion to the date of death from any cause. Patients who are alive at the time of analysis will be censored at the date of the last contact. The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTC-AE-V4.0) grade. Descriptive statistics will be provided for characterizing and assessing patient tolerance to treatment. Objective response rate is defined as the proportion of patients with complete or partial response according to RECIST 1.1. It will be summarized by a proportion together with its 95% confidence interval. The duration of response will be measured from the time of first documented response (CR or PR) until the first documented disease progression or death due to underlying cancer. Duration of response will be described in responding subjects using descriptive statistics (median, extreme values, etc.). The Time to Progression will be measured from the time of treatment start until the first documented disease progression. Patients with no event at the time of the analysis will be censored at their last tumor assessment date. The Time to treatment failure will be measured from the time of treatment start until discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death. Patients without treatment failure at the time of the analysis will be censored at their last tumor assessment. ;Timepoint(s) of evaluation of this end point: study period | — |
Countries
France
Contacts
Public ContactGwenaele Garin
Centre Leon Berard
Outcome results
None listed