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Carcinoma, Non-Small-Cell LungPhase 1BKM120NCT02128724

Palliative Thoracic Radiotherapy Plus BKM120

A Phase 1 study testing BKM120 in people with Carcinoma, Non-Small-Cell Lung, run by University of Oxford at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will test whether a drug called BKM120/buparlisib is a safe and effective treatment when given to lung cancer patients having radiotherapy treatment. The trial will identify which of three possible doses of buparlisib is best to give with lung radiotherapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
BKM120
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited Kingdom
Study dates
Apr 2013to 17 Oct 2017
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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]

Who cannot join

  • 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 %)
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  • 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 or a history of myocardial infarction within 6 months of entering the trial, congestive heart failure ( New York Heart Association functional classification III-IV) or 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. Women of child-bearing potential must have a negative serum pregnancy test less than 72 hours prior to initiating treatment

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Churchill Hospital

    Oxford, OXON, OX3 7LE

Other trials in United Kingdom

About this study

Official title: A CR-UK Phase I Study of BKM120 in Patients With Non-small Cell Lung Cancer (NSCLC) Receiving Thoracic Radiotherapy

This study will test whether a drug called BKM120/buparlisib is a safe and effective treatment when given to lung cancer patients having radiotherapy treatment. The trial will identify which of three possible doses of buparlisib is best to give with lung radiotherapy.

Read the detailed description

This study will be a single-centre, open-label, 3+3 cohort, dose escalation phase I study of the use of buparlisib in combination with thoracic radiotherapy. Patients with incurable NSCLC requiring palliative thoracic radiotherapy will be eligible for entry.

The first three cohorts of patients will be treated with escalating doses of BKM120. These patients will be treated with buparlisib for a total of fourteen days. One week after commencing buparlisib, patients will start palliative radiotherapy treatment. Radiotherapy treatment will be delivered as 20Gy in 5 fractions over a one week period. Maximum tolerated dose (MTD) will be determined and a further 6 patients will be treated at this dose. Response to buparlisib treatment will be based upon changes in tumour hypoxia and perfusion as detected by 18F-Miso PET-CT scans and perfusion CT scans respectively.

In the event that no changes are detected in tumour hypoxia or perfusion in cohorts 1-3, an optional group of patients (cohort 4) will be recruited. These patients will receive buparlisib treatment for a total of 28 days. Three weeks after commencing buparlisib, this cohort will receive palliative radiotherapy with 20Gy in 5 fractions over a one week period.

Samples from the patients will also be analysed:

Phosphorylation Status of Akt in Peripheral Blood Mononuclear Cells (PBMCs) Tumour Phosphatase and tensin homolog (PTEN) gene levels Tumour PRAS40 Levels

Being tested
BKM120
Keywords
Lung cancer, BKM120, Hypoxia, Misonidazole, Radiotherapy, Buparlisib
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Hypoxia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BKM120Drug

    Also called buparlisib

    Buparlisib is a highly specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Buparlisib is supplied as 10mg and 50mg hard gelatin capsules.

Study groups in NCT02128724
Study groupRoleWhat they receive
BKM120 plus radiotherapyExperimentalThree cohorts of patients will be treated with escalating doses of oral buparlisib. The doses will be 50mg, 80mg and 100mg, once daily. Patients will be treated with buparlisib for a total of fourteen days. One week after commencing buparlisib, patients will start palliative radiotherapy treatment. Radiotherapy treatment will be delivered as 20Gy in 5 fractions over a one week period. There will be an expansion cohort at the MTD. Patients in an optional fourth cohort will take buparlisib for 4 weeks at the MTD.
Receives: Drug: BKM120

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Escalation Analysis: Number of DLTs Observed in Evaluable Patients

    The maximum tolerated dose (MTD) was defined as the highest dose at which no more than 1 of 6 evaluable patients or 0 of 3 evaluable patients experience a dose limiting toxicity (DLT). The study was carried out using a 3+3 dose escalation design.

    DLTs were defined per NCI CTCAE v 4.0. The following were considered DLT if they occur at any point whilst the patient is on study: 1) Any ≥ grade 3 non-haematological toxicity (excluding nausea, vomiting or diarrhoea) that requires hospital admission or which does not resolve to ≤ grade 2 within 7 consecutive days of optimal treatment. 2) Any ≥ grade 3 nausea, vomiting or diarrhoea will be considered DLT only if any of them persist for >48 hours despite maximum supportive care. 3) ≥ Grade 3 pneumonitis 4) Any ≥ Grade 4 haematological toxicity. 5) Mood deterioration from baseline. DLT will be any grade ≥3 mood change if BL score of 2. DLT will be any grade ≥2 mood change if baseline score of ≤ 1.

    Measured: 8 weeks (10 weeks cohort 4 - this cohort was not opened)

  2. Safety and Tolerability Analysis: Patients With Buparlisib Related Adverse Events

    Adverse events (AEs) and Serious Adverse Events (SAEs) were also analysed for frequency. For further details, please consult the AEs/SAEs section.

    Measured: 8 weeks (10 weeks cohort 4 - this cohort was not opened)

Secondary outcomes (11)

  1. Changes in 18F-Misonidazole Uptake as Detected by PET-CT Scans: Response

    18F-Miso is a radiotracer that selectively accumulates in hypoxic tissues. 18F-Miso PET-CT scans are able to non-invasively image tumour hypoxia. A 18F-Miso PET-CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour hypoxia due to buparlisib treatment. For tumour hypoxia, a patient is classified as a 'responder' if there is evidence of a 10% or greater reduction in retained F-Misonidazole. Hypoxia was measured using TBRmean or TBRvolume (tumour-to-blood ratio).

    Measured: Days -1 and 8

  2. Blood Flow at Days -1 and 8 as Detected by Perfusion CT

    Perfusion CT is a technique used to study the vasculature within tumours and other tissues. It is non-invasive and readily incorporated into existing CT protocols using conventional contrast agents. A perfusion CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour physiology due to buparlisib treatment.

    Measured: Days -1 and 8

  3. Tumour-to-blood Volume Ratio in 18F-Misonidazole Uptake as Detected by Day -1 and Day 8 PET-CT Scans, to Investigate if Buparlisib Alters Hypoxia

    18F-Miso is a radiotracer that selectively accumulates in hypoxic tissues. 18F-Miso PET-CT scans are able to non-invasively image tumour hypoxia. A 18F-Miso PET-CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment.

    Tumour to blood volume ratio ("TBR volume") is measured by summing the number of tumour/node/metastases voxels with a value greater than or equal to 1.4.

    Measured: Days -1 and 8

  4. Changes in Blood Flow as Detected by Perfusion CT: Response

    Perfusion CT is a technique used to study the vasculature within tumours and other tissues. It is non-invasive and readily incorporated into existing CT protocols using conventional contrast agents. A perfusion CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour physiology due to buparlisib treatment. For tumour perfusion, a patient is classified as 'responder' if blood flow (BF) and/or blood volume (BV) is increased and/or mean transit time (MTT) is reduced from baseline measurements by more than 25%.

    Measured: Days -1 and 8

  5. Percentage Change in Blood Flow as Detected by Perfusion CT at Days -1 and 8

    Perfusion CT is a technique used to study the vasculature within tumours and other tissues. It is non-invasive and readily incorporated into existing CT protocols using conventional contrast agents. A perfusion CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour physiology (blood flow) due to buparlisib treatment, and the percentage change between both scans calculated.

    Measured: Days -1 and 8

  6. Tumour-to-blood Mean Ratio in 18F-Misonidazole Uptake as Detected by PET-CT Scans, to Investigate if Buparlisib Alters Hypoxia

    18F-Miso is a radiotracer that selectively accumulates in hypoxic tissues. 18F-Miso PET-CT scans are able to non-invasively image tumour hypoxia. A 18F-Miso PET-CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour hypoxia due to buparlisib treatment.

    Hypoxia was measured using TBRmean and TBRvolume (tumour-to-blood ratio mean, tumour-to-blood ratio volume).

    TBR mean is measured by dividing all tumour/node/metastases voxels by the mean value of the descending aorta activity concentration.

    Measured: Days -1 and 8

  7. Tumour-to-blood Volume Ratio Percentage Changes Between Day -1 and Day 8 in 18F-Misonidazole Uptake as Detected by PET-CT Scans, to Investigate if Buparlisib Alters Hypoxia

    18F-Miso is a radiotracer that selectively accumulates in hypoxic tissues. 18F-Miso PET-CT scans are able to non-invasively image tumour hypoxia. A 18F-Miso PET-CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour hypoxia due to buparlisib treatment. The percentage change between the TBR volume for the 1st and 2nd scans was calculated.

    TBR volume is measured by summing the number of tumour/node/metastases voxels with a value greater than or equal to 1.4.

    Hypoxia was measured using TBRmean and TBRvolume (tumour-to-blood ratio mean, tumour-to-blood ratio volume).

    Measured: Days -1 and 8

  8. Percentage Changes in Blood Volume Between Day -1 and Day 8 as Detected by Perfusion CT

    Perfusion CT is a technique used to study the vasculature within tumours and other tissues. It is non-invasive and readily incorporated into existing CT protocols using conventional contrast agents. A perfusion CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour physiology due to buparlisib treatment, and the % change between the 2 scans calculated.

    Measured: Days -1 and 8

  9. Blood Volume at Day -1 and Day 8 as Detected by Perfusion CT

    Perfusion CT is a technique used to study the vasculature within tumours and other tissues. It is non-invasive and readily incorporated into existing CT protocols using conventional contrast agents. A perfusion CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour physiology due to buparlisib treatment

    Measured: Days -1 and 8

  10. Mean Transit Time as Detected by Perfusion CT at Days -1 and 8

    Perfusion CT is a technique used to study the vasculature within tumours and other tissues. It is non-invasive and readily incorporated into existing CT protocols using conventional contrast agents. A perfusion CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour physiology (blood flow) due to buparlisib treatment.

    Measured: Days -1 and 8

  11. Percentage Change in Mean Transit Time as Detected by Perfusion CT at Days -1 and 8

    Perfusion CT is a technique used to study the vasculature within tumours and other tissues. It is non-invasive and readily incorporated into existing CT protocols using conventional contrast agents. A perfusion CT scan was conducted prior to commencing buparlisib and repeated prior to commencing radiotherapy treatment to identify changes in tumour physiology (blood flow) due to buparlisib treatment, and the % change between the 2 scans was calculated.

    Measured: Days -1 and 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2014 (estimated)
  2. Study startApr 2013
  3. Primary completion17 Oct 2017
  4. Study completion17 Oct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02128724
Sponsor's protocol ID
OCTO_031
Other IDs
2012-003762-40
Acronym
BKM120
Status last verified
Nov 2017
First submitted
16 Apr 2014
Last updated
1 Aug 2019
Data monitoring committee
Yes

Publications

  • Fokas E, Im JH, Hill S, Yameen S, Stratford M, Beech J, Hackl W, Maira SM, Bernhard EJ, McKenna WG, Muschel RJ. Dual inhibition of the PI3K/mTOR pathway increases tumor radiosensitivity by normalizing tumor vasculature. Cancer Res. 2012 Jan 1;72(1):239-48. doi: 10.1158/0008-5472.CAN-11-2263. Epub 2011 Nov 22.

    PubMed 22108822

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BKM120 in people with Carcinoma, Non-Small-Cell Lung, run by University of Oxford at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation Analysis: Number of DLTs Observed in Evaluable Patients (time frame: 8 weeks (10 weeks cohort 4 - this cohort was not opened)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02128724, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2019.

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Palliative Thoracic Radiotherapy Plus BKM120 | AzTrials