Condition category
Cancer
Date applied
25/01/2013
Date assigned
29/01/2013
Last edited
19/07/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Ms Stasya Ng

ORCID ID

Contact details

Old Road Campus
Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom
-
octo-bkm210@oncology.ox.ac.uk

Additional identifiers

EudraCT number

2012-003762-40

ClinicalTrials.gov number

NCT02128724

Protocol/serial number

13615

Study information

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

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.

Ethics approval

NRES Committee South Central - Oxford B, 07/01/2013, ref: 12/SC/0674

Study design

Non-randomised open-label 3+3 cohort dose-escalation phase I study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Lung Cancer; Disease: Lung (non-small cell)

Intervention

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)

Intervention type

Drug

Phase

Phase I

Drug names

BKM120

Primary outcome measures

To determine the safety, dose-limiting toxicity (DLT) and MTD of BKM120 with radiotherapy

Secondary outcome measures

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 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. 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 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

Overall trial start date

31/03/2013

Overall trial end date

30/04/2017

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 19/07/2016:
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 0-1
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 <= 1.5 x ULN
8.9. Fasting plasma glucose (FPG) <= 120mg/dL [6.7 mmol/L]

Previous 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 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) 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]

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 2-30

Participant 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 III-IV)
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. Women of childbearing potential must have a negative serum pregnancy test <= 72 hours prior to initiating treatment

Recruitment start date

31/03/2013

Recruitment end date

31/12/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Churchill Hospital
Oxford
OX3 7LE
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trials and Research Governance (CTRG)
Joint Research Office
Block 60 Churchill Hospital
Headington
OX3 7LJ
United Kingdom

Sponsor type

University/education

Website

http://www.admin.ox.ac.uk/researchsupport/ctrg/

Funders

Funder type

Charity

Funder name

Cancer Research UK (UK)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Oxford Cancer Imaging Centre (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

30/04/2018

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

28/05/2015: the overall trial end date was changed from 30/08/2016 to 30/04/2017. 15/05/2015: the overall trial end date was changed from 30/06/2014 to 30/08/2016.