Topic: National Cancer Research Network
Conditions
Interventions
BKM120 Cohort 1, 50 mg OD (days 1-14). 20 Gy in 5 fractions (days 8-14)
BKM120 Cohort 2, 80 mg OD (days 1-14). 20 Gy in 5 fractions (days 8-14)
BKM120 Cohort 3, 100 mg
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 02/03/2017: 1. Evidence of histologically confirmed NSCLC of any stage 2. Thoracic lesion requiring palliative radiotherapy and which has been identified on a scan within eight weeks of starting the trial 3. Male or female, age >= 18 years at the day of consenting to the study 4. Life expectancy of at least 16 weeks 5. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2 6. Patient is able to swallow and retain oral medication 7. 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 8. Haematological and biochemical indices within the ranges shown below: 8.1. Haemoglobin (Hb) >= 9.0 g/dL 8.2. Absolute neutrophil count >= 1.5 x 109/L 8.3. Platelet count >=100 x 109/L 8.4. International Normalised Ratio (INR) = 18 years at the day of consenting to the study 4. Life expectancy of at least 16 weeks 5. Eastern Cooperative Oncology Group (ECOG) performance score of 0-1 6. Patient is able to swallow and retain oral medication 7. 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 8. Haematological and biochemical indices within the ranges shown below: 8.1. Haemoglobin (Hb) >= 9.0 g/dL 8.2. Absolute neutrophil count >= 1.5 x 109/L 8.3. Platelet count >=100 x 109/L 8.4. International Normalised Ratio (INR) <= 1.5 8.5. Potassium, calcium and Magnesium Within normal range 8.6. Alanine aminotranferease (ALT) and aspartate aminotransferase (AST) not above normal range or< =3.0 times ULN if liver metastases are present 8.7. 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 chief investigator is satisfied that the patient has well documented Gilbert’s disease and absence of other contributing disease process at the time of diagnosis 8.8. Creatinine <= 1
Exclusion criteria
Exclusion criteria: 1. Previous chemotherapy or biological therapy within four weeks of starting study treatment 2. Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment 3. Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy 4. 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. 5. 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). 6. Patient has poorly controlled diabetes mellitus (HbA1c > 8 %) 7. Previous exposure to PI3K, mTOR, or AKT inhibitor 8. Patient has a known hypersensitivity to any of the excipients of BKM120 9. Previous thoracic radiotherapy treatment 10. Any previous extra-thoracic radiotherapy within 28 days prior to enrolment 11. 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 12 .Patient meets the cut-off score of >= 12 in the PHQ9 or a cut-off of >= 15 in the GAD7 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 PHQ9 (independent of the total score of the PHQ9) 13. Patient has >=CTCAE grade 3 anxiety 14. 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. 15 .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) 16. Patient has had major surgery within 14 days of starting the study drug. 17. 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). 18. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120. 19. Patients who are known to be serologically positive for Hep B, Hep C or HIV. 20. Patient has active cardiac disease including any of the following: 20.1. LVEF 480 msec on screening ECG (using the QTcF formula) 20.3. Patient is taking a medication that has a known risk of causing QT interval prolongation or inducing Torsa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safety, dose-limiting toxicity (DLT) and MTD of BKM120 with radiotherapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 19/07/2016: 1. To evaluate Akt phosphorylation as a predictive marker of response to BKM120; Timepoint(s): Determine phosphorylation status of Akt in peripheral blood mononuclear cells (PBMC) at baseline, during BKM120 treatment and following BKM120 + RT treatment 2. To investigate potential biomarkers that correlate with response to BKM120; Timepoint(s): Measure tumour pAkt and Phosphatase and tensin homolog (PTEN) levels and then identify mutation status of RAS, PI3K and EGFR by PCR 3. To investigate whether BKM120 alters tumour hypoxia and perfusion; Timepoint(s): Changes in 18F-Misonidazole uptake as detected by PET-CT scans. Changes in blood flow as detected by perfusion CT Previous secondary outcome measures: 1. To evaluate Akt phosphorylation as a predictive marker of response to BKM120; Timepoint(s): Determine phosphorylation status of Akt in peripheral blood mononuclear cells (PBMC) at baseline, during BKM120 treatment and following BKM120 + RT treatment 2. To investigate potential biomarkers that correlate with response to BKM120; Timepoint(s): Measure tumour pAkt and Phosphatase and tensin homolog (PTEN) levels and then identify mutation status of RAS, PI3K and EGFR by PCR 3. To investigate whether BKM120 alters tumour hypoxia and perfusion; Timepoint(s): Changes in 18F-Misonidazole uptake as detected by PET-CT scans | — |
Countries
United Kingdom
Outcome results
None listed