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Head and Neck NeoplasmsPhase 2PIK-ORLNCT01737450

Activity and Safety Study of BKM120 in Monotherapy in Patient With Metastatic Head and Neck Cancer Recurrent or Progressive

A Phase 2 study testing BKM120 in people with Head and Neck Neoplasms and Neoplasm Metastasis, run by Centre Leon Berard at 9 sites in France.

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

The aim of this study is to determine the activity, to assess the safety and tolerance of BKM120 in adult patients with recurrent or metastatic head and neck cancer progressive under platin and cetuximab-based chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older
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
58 participants
Where
9 sitesFrance
Study dates
Jan 2013to Mar 2019
Phase
Phase 2
Are there results?
None posted in the registry

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

  • 1. Adult men and women ≥ 18 years at the day of inform consent signature.
  • 2. Patients with metastatic or relapsed squamous cell head and neck carcinoma .
  • 3. Documented progression or relapse after platin and cetuximab or anti-epidermal growth factor receptor (EGFR) -based chemotherapy at time of study drug start
  • 4. Documented mutational status of PIK3CA before study drug start
  • 5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 .
  • 6. At least one measurable lesion by CT-scan as per RECIST 1.1 .
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  • 7. Life expectancy > 12 weeks.
  • 8. Patients must be able to swallow capsules.
  • 9. Adequate bone marrow, renal and liver function as defined by the following tests :
  • Absolute neutrophil count ≥ 1.0 x 109/L,
  • Platelet count > 100 x 109/L,
  • Haemoglobin value above 9 g/dL,
  • international normalized ratio (INR) ≤ 1.5
  • Serum Creatinine ≤ 1.5 upper limit of normal (ULN)
  • Glomerular filtration rate calculated using Cockcroft-Gault formula > 60ml/min (or MDRD formula for patients older than 65 years)
  • Potassium, calcium, magnesium within normal limits for the institution
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < ULN (or < 3.0 x ULN if liver metastases are present))
  • Serum bilirubin within normal range (or ≤ 1.5 ULN if liver metastases are present; or total bilirubin ≤ 3.0 ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
  • Fasting plasma glucose (FPG) ≤ 120 mg/dL or ≤ 6.7 mmol/L.
  • 10. Women of childbearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test within ≤ 72 hours before initiating study treatment) must agree to use two methods of medically acceptable forms of contraception during the whole treatment period and for 1 month (= 5 x t½ of BKM120) after the last treatment intake.
  • 11. Fertile males must use a highly effective contraception during dosing of any study agent + [5 x t1/2] + 12 weeks = contraception through 16 weeks after final dose of study therapy and should not father a child in this period. Female partner of male study subject: highly effective contraception during dosing of study agent + 4 weeks after final dose of study therapy
  • 12. Patient should be able and willing to comply with study visits and procedures as per protocol.
  • 13. Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.
  • 14. Patients must be covered by a medical insurance.

Who cannot join

  • 1. Patient having received previous treatment with PI3K and/or mammilian target of rapamycin (mTOR) inhibitors.
  • 2. Patient with symptomatic central nervous system (CNS) metastases.
  • 3. Patient with a concurrent malignancy or has a malignancy within 3 years of study enrollment, (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer).
  • 4. Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist:
  • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others),
  • Patients with active severe personality disorders (defined according to Diagnostic and Statistical Manual (DSM) - IV) are not eligible.
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  • Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
  • ≥ CTCAE grade 3 anxiety,
  • or meets the cut-off score of ≥ 12 in the Patient Health Questionnaire (PHQ) -9 or a cut-off of ≥ 15 in the generalized anxiety disorder (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).
  • 5. Patient concurrently using other approved or investigational anti-neoplasic agent.
  • 6. Patient who has received anticancer therapy < 2 weeks or investigational treatment < 4 weeks prior the initiation of study drug.
  • 7. Patient who has received radiotherapy ≤ 4 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia).
  • 8. Patient having had major surgery within 14 days prior to starting study drug or has not recovered from major side effects of the surgery.
  • 9. Patient with poorly controlled diabetes mellitus (i.e. HbA1c > 8 %)
  • 10. Patient with 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),
  • corrected QT interval (QTc) > 480 (female) or 470 msec (male) on screening ECG (using the corrected QT Fridericia (QTcF) formulae),
  • Angina pectoris that requires the use of anti-anginal medication,
  • Ventricular arrhythmias except for benign premature ventricular contractions,
  • Supraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication,
  • Conduction abnormality requiring a pacemaker,
  • Valvular disease with documented compromise in cardiac function,
  • Symptomatic pericarditis.
  • 11. Patient with a history of cardiac dysfunction including any of the following:
  • Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function,
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV),
  • Documented cardiomyopathy,
  • Other cardiac arrhythmia not controlled with medication.
  • 12. Patient currently receiving treatment with QT prolonging medication known to have a risk to induce Torsades de Pointes, and if the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
  • 13. Patient with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120
  • 14. Patient receiving chronic treatment (> 5 days) with steroids or another immunosuppressive agent. Note: Topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular) are allowed. Patients with previously treated brain metastases, who are on a stable low dose corticosteroids treatment (e.g., dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment, are eligible.
  • 15. Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate her participation in the clinical study
  • 16. Patient has a history of non-compliance to medical regimen.
  • 17. Patient is currently being treated with drugs known to be strong inhibitors or inducers of isoenzyme Cytochrome P450 family 3 subfamily A member 4 (CYP3A), and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
  • 18. Patient has a known history of HIV infection.
  • 19. Pregnant or nursing (lactating) woman.
  • 20. Patient has a known hypersensitivity to any of the excipients of BKM120.
  • 21. Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy.
  • 22. Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin, or fondaparinux is allowed.
  • 23. Patient has acute viral hepatitis or a history of chronic or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, typically defined by elevated AST/ALT (persistent or intermittent), high HBV DNA level, HBsAg positive, or high HCV RNA level (testing not mandatory)

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

France9 sites

  • Hopital St André

    Bordeaux

  • Hôpital BEAUJON

    Clichy

  • Centre Oscar Lambret

    Lille

  • Centre Léon Bérard

    Lyon

  • Centre Val d'Aurelle - Paul Lamarque

    Montpellier

  • Centre Antoine LACASSAGNE

    Nice

  • Institut Curie

    Paris

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69003

  • Institut Gustave Roussy

    Villejuif

Other trials in France

About this study

Official title: A Phase II, Multicenter Trial Aiming to Evaluate the Clinical Interest of a Monotherapy With BKM120 , a Phosphoinositide 3-kinase (PI3K) Inhibitor in Patient With Metastatic Head and Neck Cancer Recurrent or Progressive Under Platin and Cetuximab-based Chemotherapy

The aim of this study is to determine the activity, to assess the safety and tolerance of BKM120 in adult patients with recurrent or metastatic head and neck cancer progressive under platin and cetuximab-based chemotherapy.

Read the detailed description

BKM120 is a PI3K inhibitor. The PI3K/Protein kinase B (AKT) signalling pathway deregulation is frequently observed in Head and neck cancer. In addition to its role in tumor genesis, the PI3K/AKT pathway seems to be involved in resistance to cetuximab.

In this context, the study proposal is to evaluate the clinical interest of a monotherapy with a PI3K inhibitor (BKM120, Novartis) in patients with metastatic head and neck cancers refractory or relapsing under platin and cetuximab based- chemotherapy. Since resistance to cetuximab can result from phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, PIK3CA amplification or mutation upstream in the PI3K pathway, BKM120 activity will be evaluated in two parallel independent cohorts of patients: patients presenting a PI3KCA mutation and patients without a PI3KCA mutation.

Being tested
BKM120
Keywords
Metastatic head and neck cancer, PI3K inhibitor, Recurrent head and meck cancer, Progressive head and neck cancer, BKM120
Medical subject headings
Head and Neck Neoplasms, Neoplasm Metastasis, Recurrence, Disease Progression

What participants receive

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

  • BKM120Drug

    Also called Buparlisib

Study groups in NCT01737450
Study groupRoleWhat they receive
BKM120ExperimentalFull dose=100 mg/day (oral route) One study cycle equals 28 days. Patients will be treated until disease progression, unacceptable toxicity, or willingness to stop.
Receives: Drug: BKM120

What is being measured

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

  1. 2 months disease control rate

    Control rate= Complete response, partial response and stable disease according to RECIST 1.1

    Measured: 2 months after the first BKM120 intake

Secondary outcomes (6)

  1. Progression free survival

    Measured: At 2 months, 4 months and then every 2 months

  2. Overall survival (OS)

    OS will be measured from the date of inclusion to the date of death from any cause.

    Measured: Baseline, at 2 months, 4 months and then every 2 months at the end of Study

  3. Safety

    The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria adverse event (CTCAE) V4.0 grade.

    Measured: continuous up to 30 days after the last treatment

  4. Objective response rate

    Objective response rate is defined as the proportion of patient with complete or partial response according RECIST 1.1

    Measured: At Baseline, 2 months, 4 months and then every 2 months, at the end of Study

  5. Duration of response

    The duration of response will be measured from the time of first documented response until the first documented disease progression or death due to underlying cancer.

    Measured: At Baseline, 2 months, 4months and then every 2 months, at the end of Study

  6. Time to Progression

    Time to Progression will be measured from the time of treatment start until the first documented disease progression. Patients with no event at the time of the analysis will be censored at their last tumor assessment date.

    Measured: At Baseline, 2 months, 4months and then every 2 months, at the end of Study

Timeline

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

  1. First posted29 Nov 2012 (estimated)
  2. Study startJan 2013
  3. Primary completionSep 2018
  4. Study completionMar 2019

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01737450
Sponsor's protocol ID
ET12-034
Other IDs
2012-002403-18
Acronym
PIK-ORL
Status last verified
Jun 2019
First submitted
13 Nov 2012
Last updated
24 Jun 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Graupera M, Guillermet-Guibert J, Foukas LC, Phng LK, Cain RJ, Salpekar A, Pearce W, Meek S, Millan J, Cutillas PR, Smith AJ, Ridley AJ, Ruhrberg C, Gerhardt H, Vanhaesebroeck B. Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature. 2008 May 29;453(7195):662-6. doi: 10.1038/nature06892. Epub 2008 Apr 30.

    PubMed 18449193

  • Schnell CR, Stauffer F, Allegrini PR, O'Reilly T, McSheehy PM, Dartois C, Stumm M, Cozens R, Littlewood-Evans A, Garcia-Echeverria C, Maira SM. Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging. Cancer Res. 2008 Aug 15;68(16):6598-607. doi: 10.1158/0008-5472.CAN-08-1044.

    PubMed 18701483

  • Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med. 1993 Jan 21;328(3):184-94. doi: 10.1056/NEJM199301213280306. No abstract available.

    PubMed 8417385

  • Saranath D, Panchal RG, Nair R, Mehta AR, Sanghavi VD, Deo MG. Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer. Eur J Cancer B Oral Oncol. 1992 Oct;28B(2):139-43. doi: 10.1016/0964-1955(92)90043-z.

    PubMed 1306731

  • Burtness B. The role of cetuximab in the treatment of squamous cell cancer of the head and neck. Expert Opin Biol Ther. 2005 Aug;5(8):1085-93. doi: 10.1517/14712598.5.8.1085.

    PubMed 16050785

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BKM120 in people with Head and Neck Neoplasms and Neoplasm Metastasis, run by Centre Leon Berard at 9 sites in France.

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 24 inclusion and 41 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 24 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

2 months disease control rate (time frame: 2 months after the first BKM120 intake). 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 NCT01737450, which also lists 5 linked publications.

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 24 Jun 2019.

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