Activity and Safety Study of BKM120 in Monotherapy in Patient With Metastatic Head and Neck Cancer Recurrent or Progressive (PIK-ORL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01737450
Recruitment Status : Recruiting
First Posted : November 29, 2012
Last Update Posted : July 26, 2017
National Cancer Institute, France
Fondation ARC
Information provided by (Responsible Party):
Centre Leon Berard

Brief 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.

Condition or disease Intervention/treatment Phase
Head and Neck Neoplasms Neoplasm Metastasis Recurrent Disease Progressive Disease Drug: BKM120 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2013
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BKM120
Full 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.
Drug: BKM120
Other Name: Buparlisib

Primary Outcome Measures :
  1. 2 months disease control rate [ Time Frame: 2 months after the first BKM120 intake ]
    Control rate= Complete response, partial response and stable disease according to RECIST 1.1

Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: At 2 months, 4 months and then every 2 months ]
  2. Overall survival (OS) [ Time Frame: Baseline, at 2 months, 4 months and then every 2 months at the end of Study ]
    OS will be measured from the date of inclusion to the date of death from any cause.

  3. Safety [ Time Frame: continuous up to 30 days after the last treatment ]
    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.

  4. Objective response rate [ Time Frame: At Baseline, 2 months, 4 months and then every 2 months, at the end of Study ]
    Objective response rate is defined as the proportion of patient with complete or partial response according RECIST 1.1

  5. Duration of response [ Time Frame: At Baseline, 2 months, 4months and then every 2 months, at the end of Study ]
    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.

  6. Time to Progression [ Time Frame: At Baseline, 2 months, 4months and then every 2 months, at the end of Study ]
    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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 .
  • 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.

Exclusion Criteria:

  • 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.

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01737450

Contact: Jérôme FAYETTE, MD

Hopital St André Recruiting
Bordeaux, France
Contact: Alain Ravaud    05 56 79 58 08   
Principal Investigator: Alain RAVAUD         
Sub-Investigator: Laurence DIGUE         
Sub-Investigator: Amaury DASTE         
Sub-Investigator: Denis SMITH         
Sub-Investigator: Nathalie TRUFFLANDIER         
Hôpital BEAUJON Not yet recruiting
Clichy, France
Contact: Sandrine FAIVRE, MD   
Principal Investigator: Sandrine FAIVRE, MD         
Centre Oscar Lambret Recruiting
Lille, France
Contact: Nuria KOTECKI, MD    +33 3 20 29 59 11   
Contact: Gautier LEFEBVRE    +33 3 20 29 59 54   
Sub-Investigator: Audrey MAILLIEZ, MD         
Sub-Investigator: Gautier LEFEVBRE, MD         
Principal Investigator: Nuria KOTECKI, MD         
Centre Léon Bérard Recruiting
Lyon, France
Contact: Jérome FAYETTE, MD   
Principal Investigator: Jérôme FAYETTE, MD         
Sub-Investigator: Virginie AVRILLON, MD         
Sub-Investigator: Philippe CASSIER, MD         
Sub-Investigator: Alice LEVARD, MD         
Sub-Investigator: Eve-Marie NEIDHARDT, MD         
Sub-Investigator: Valérie PAULUS, MD         
Sub-Investigator: Philippe TOUSSAINT, MD         
Centre Val d'Aurelle - Paul Lamarque Recruiting
Montpellier, France
Contact: Didier CUPISSOL, MD   
Sub-Investigator: Catherine FAVIER, MD         
Principal Investigator: Didier CUPISSOL, MD         
Sub-Investigator: Dalila FERROUKHI, MD         
Sub-Investigator: Maryline LAIGRE, MD         
Sub-Investigator: Ernesto Jose LOPEZ MARTINEZ, MD         
Centre Antoine LACASSAGNE Recruiting
Nice, France
Contact: Frédéric PEYRADE, MD   
Principal Investigator: Frédéric PEYRADE, MD         
Sub-Investigator: Christophe HEBERT, MD         
Sub-Investigator: Esma SAADA-BOUZID, MD         
Sub-Investigator: Jérôme BARRIERE, MD         
Sub-Investigator: Delphine BORCHIELLINI, MD         
Institut Curie Recruiting
Paris, France
Contact: Christophe LETOURNEAU, MD   
Principal Investigator: Christophe LE TOURNEAU, MD         
Sub-Investigator: Véronique DIERAS, MD         
Sub-Investigator: Marie-Paule SABLIN, MD         
Centre Hospitalier Lyon Sud Recruiting
Pierre Benite, France, 69003
Contact: Benoît YOU    04 78 86 43 18   
Principal Investigator: Benoît YOU         
Sub-Investigator: Amandine BRUYAS         
Sub-Investigator: Gilles FREYER         
Sub-Investigator: Salima HAMIZI         
Sub-Investigator: Sophie TARTAS         
Institut Gustave Roussy Recruiting
Villejuif, France
Contact: Caroline EVEN, MD    +33 1 42 11 46 17   
Contact: François-Régis FERRAND, MD   
Principal Investigator: Caroline EVEN, MD         
Sub-Investigator: François-Régis FERRAND, MD         
Sub-Investigator: Margarida MATIAS, MD         
Sub-Investigator: Alfred SCHILF, MD         
Sub-Investigator: Lamia MAYACHE-BADIS, MD         
Sponsors and Collaborators
Centre Leon Berard
National Cancer Institute, France
Fondation ARC
Principal Investigator: Jérome FAYETTE, MD Centre Léon Bérard, Lyon- FRANCE

Responsible Party: Centre Leon Berard Identifier: NCT01737450     History of Changes
Other Study ID Numbers: ET12-034
2012-002403-18 ( EudraCT Number )
First Posted: November 29, 2012    Key Record Dates
Last Update Posted: July 26, 2017
Last Verified: July 2017

Keywords provided by Centre Leon Berard:
Metastatic head and neck cancer
PI3K inhibitor
Recurrent head and meck cancer
Progressive head and neck cancer

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasm Metastasis
Disease Progression
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Disease Attributes