Sponsor: University of Oxford
EudraCT number: 2012-003762-40
A CR-UK phase I study of BKM120 in patients with non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy.
To determine the safety, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of BKM120 when administered concomitantly with thoracic radiotherapy in patients with metastatic NSCLC.
Open to recruitment.
This is a single centre study active at the Churchill Hospital (Oxford) only.
Target recruitment: 2-30 patients presenting with any stage of NSCLC, requiring palliative radiotherapy treatment.
Current Recruitment: 17 Patients (March 2017).
Currently recruiting to the expansion phase.
- Evidence of histologically confirmed NSCLC of any stage
- Thoracic lesion requiring palliative radiotherapy and which has been identified on a scan within eight weeks of starting the trial.
- Male or female, age ≥ 18 years at the day of consenting to the study.
- Life expectancy of at least 16 weeks.
- ECOG performance score of 0-2.
- Patient is able to swallow and retain oral medication.
- The patient is willing to provide written informed consent and is likely to comply with the protocol for the duration of the study, and scheduled follow-up visits and examinations.
- Haematological and biochemical indices within the ranges shown below:
- Haemoglobin (Hb) ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1.5 x 109/L
- Platelet count ≥100 x 109/L
- International Normalised Ratio (INR) ≤ 1.5
- Potassium, calcium and Magnesium within normal range
- ALT and AST not above normal range or ≤3.0 times ULN if liver metastases are present
- Total serum bilirubin not above normal range, or ≤1.5 times ULN if liver metastases are present or total bilirubin ≤3.0 times ULN if the patient has well documented Gilbert’s disease and absence of other contributing disease process at the time of diagnosis
- Creatinine ≤ 1.5 x ULN
- Fasting plasma glucose (FPG) ≤ 120mg/dL [6.7 mmol/L]
- Previous chemotherapy or biological therapy within four weeks of starting study treatment.
- Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment.
- Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy.
- Treatment at the start of study treatment with any drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A4, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
- Presence of active uncontrolled or symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this trial. Any prior local treatment for CNS metastases must have been completed treatment ≥ 28 days prior to enrolment in the trial (including surgery and radiotherapy).
- Patient has poorly controlled diabetes mellitus (HbA1c > 8 %)
- Previous exposure to PI3K, mTOR, or AKT inhibitor
- Patient has a known hypersensitivity to any of the excipients of BKM120
- Previous thoracic radiotherapy treatment
- Any previous extra-thoracic radiotherapy within 28 days prior to enrolment
- Medically documented history of or active major depressive episode, bipolar disorder, obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or risk of doing harm to others
- Patient meets the cut-off score of ≥ 12 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or 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)
- Patient has ≥CTCAE grade 3 anxiety
- Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.
- Patient has a concurrent malignancy or has had any malignancy (other than NSCLC) in the last 3 years prior to start of study treatment (with the exception of adequately treated basal or squamous cell carcinoma or cervical carcinoma in situ)
- Patient has had major surgery within 14 days of starting the study drug.
- Patient has any other concurrent severe, and/or uncontrolled medical condition that would, in the investigator’s judgement contraindicate patient participation in the clinical study (e.g. chronic pancreatitis, chronic active hepatitis).
- Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120.
- Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
- Patient has active cardiac disease including any of the following:
- Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
- QTc > 480 msec on screening ECG (using the QTcF formula)
- Patient is taking a medication that has a known risk of causing QT interval prolongation or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to an alternative medication.
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Any other cardiac arrhythmia not controlled with medication
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with documented compromise in cardiac function
- Symptomatic pericarditis
- History of myocardial infarction within 6 months of entering the trial
- History of congestive heart failure( New York Heart Association functional classification III-IV)
- Documented cardiomyopathy
- Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used. Oral contraception, injected or implanted hormonal methods are not allowed as BKM120 potentially decreases the effectiveness of hormonal contraceptives. Acceptable methods of contraception are either:
- True abstinence
- Surgical sterilization
- Male partner sterilization
- Or use of a combination of any two of the following (a+b):
a) Placement of an intrauterine device (IUD) or intrauterine system (IUS)
b) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
Women of child-bearing potential must have a negative serum pregnancy test ≤ 72 hours prior to initiating treatment.
- To determine the safety, dose-limiting toxicity (DLT) and MTD of BKM120 when administered concomitantly with thoracic radiotherapy in patients with incurable NSCLC
- To investigate whether BKM120 alters tumour hypoxia and perfusion
- To evaluate Akt phosphorylation as a predictive marker of response to BKM120
- To investigate potential biomarkers that correlate with response to BKM120
Data submission for this trial is via electronic submission of data in OpenClinica.