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21 March 2013
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| [ Print-friendly version ] |
| A CR-UK phase I study of BKM120 in patients with non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy |
| ISRCTN | ISRCTN04813360 |
| DOI | 10.1186/ISRCTN04813360 |
| ClinicalTrials.gov identifier | |
| EudraCT number | 2012-003762-40 |
| Public title | A CR-UK phase I study of BKM120 in patients with non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy |
| Scientific title | A CR-UK phase I dose escalation study of BKM120 in patients with non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy |
| Acronym | BKM120 |
| Serial number at source | 13615 |
| Study hypothesis |
This study will be a single-centre, open-label, 3+3 cohort, dose escalation phase I study of the use of BKM120 in combination with thoracic radiotherapy. Patients with incurable NSCLC requiring palliative thoracic radiotherapy will be eligible for entry.
More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13615 |
| Lay summary | Lay summary under review with external organisation |
| Ethics approval | NRES Committee South Central - Oxford B, 7th January 2013, ref: 12/SC/0674 |
| Study design | Non-randomised open-label 3+3 cohort dose escalation phase I study |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Topic: National Cancer Research Network; Subtopic: Lung Cancer; Disease: Lung (non-small cell) |
| Participants - inclusion criteria |
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 01 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) within normal range or< =3.0 times ULN if liver metastases are present 8.7. Total serum bilirubin within 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 <= 1.5 x ULN 8.9. Fasting plasma glucose (FPG) <= 120mg/dL [6.7 mmol/L] |
| Participants - 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 < 50% as determined by MUGA scan or ECHO 20.2. QTc > 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 Torsades de Pointes, and the treatment cannot be discontinued or switched to an alternative medication. 20.4. Angina pectoris that requires the use of antianginal medication 20.5. Ventricular arrhythmias except for benign premature ventricular contractions 20.6. Any other cardiac arrhythmia not controlled with medication 20.7. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication 20.8. Conduction abnormality requiring a pacemaker 20.9. Valvular disease with documented compromise in cardiac function 20.10. Symptomatic pericarditis 20.11. History of myocardial infarction within 6 months of entering the trial 20.12. History of congestive heart failure( New York Heart Association functional classification IIIIV) 20.13. Documented cardiomyopathy 21.Pregnant or breastfeeding women, or women of childbearing potential unless effective methods of contraception are used. Women of childbearing potential must use highly effective methods of contraception. 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: 21.1. True abstinence 21.2. Surgical sterilization 21.3. Male partner sterilization Or use of a combination of any two of the following (a+b): a) Placement of an IUD or IUS b) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidalfoam/gel/film/cream/vaginal suppository . Female patients must use acceptable methods of contraception must continue to use contraception for at least 4 weeks after completing BKM120. Male patients (and their female partners) will need to continue to use use contraception for at least 16 weeks after completing BKM120. 22. Women of childbearing potential must have a negative serum pregnancy test <= 72 hours prior to initiating treatment |
| Anticipated start date | 31/03/2013 |
| Anticipated end date | 30/06/2014 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | UK Sample Size: 2-30 |
| Interventions |
BKM120 Cohort 1, 50 mg OD (days 1-14). 20 Gy in 5 fractions (days 8-14)
BKM120 Cohort 2, 80mg OD (days 1-14). 20 Gy in 5 fractions (days 8-14) BKM120 Cohort 3, 100mg OD (days 1-14). 20 Gy in 5 fractions (days 8-14) BKM120 Cohort 4, At maximum tolerated dose (MTD) (days 1 to 28). 20 Gy in 5 fractions (days 22 – 28) |
| Primary outcome measure(s) | To determine the safety, dose-limiting toxicity (DLT) and MTD of BKM120 with radiotherapy |
| Secondary outcome measure(s) |
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 B
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. |
| Sources of funding |
1. Cancer Research UK (UK)
2. Oxford Cancer Imaging Centre (UK) |
| Trial website | |
| Publications | |
| Contact name | Ms Linda Collins |
| Address |
Old Road Campus
Roosevelt Drive Headington |
| City/town | Oxford |
| Zip/Postcode | OX3 7DQ |
| Country | United Kingdom |
| Linda.Collins@oncology.ox.ac.uk | |
| Sponsor | University of Oxford (UK) |
| Address |
Clinical Trials and Research Governance (CTRG)
Joint Research Office Block 60 Churchill Hospital |
| City/town | Headington |
| Zip/Postcode | OX3 7LJ |
| Country | United Kingdom |
| Sponsor website: | http://www.admin.ox.ac.uk/researchsupport/ctrg/ |
| Date applied | 25/01/2013 |
| Last edited | 08/03/2013 |
| Date ISRCTN assigned | 29/01/2013 |
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| © 2013 ISRCTN unless otherwise stated. | |
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