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

Phase 2
18 Years
Open (Enrolling)
Head and Neck Neoplasms, Neoplasm Metastasis, Recurrent Disease, Progressive Disease

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Trial Information

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

BKM120 is a PI3K inhibitor. The PI3K/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 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.

Inclusion Criteria:

- Adult men and women ≥ 18 years at the day of inform consent signature.

- Patients with metastatic or relapsed head and neck cancer.(oropharynx, oral cavity,
hypopharynx and larynx). Patients with cancer of nasopharynx (i.e. cavum cancer) are
not eligible

- Documented progression or relapse after platin and cetuximab-based chemotherapy
(combination or sequential treatment).

- Documented mutational status of PIK3CA before inclusion (molecular pre-screening).

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- At least one measurable lesion by CT-scan as per RECIST 1.1

- Life expectancy > 12 weeks.

- Patients must be able to swallow capsules.

- Adequate bone marrow, renal and liver function as defined by the following tests (to
be carried out 7 days prior to starting 1st treatment cycle):

- Absolute neutrophil count ≥ 1.0 x 109/L,

- Platelet count > 100 x 109/L,

- Haemoglobin value above 9 g/dL,

- INR ≤ 1.5

- Serum Creatinine ≤ 1.5 ULN

- Glomerular filtration rate calculated using Cockcroft-Gault formula > 60ml/min
(or MDRD formulae for patients older than 65 years)

- Potassium, calcium, magnesium within normal limits for the institution

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within
normal range (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.

- 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.

- 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

- Patient should be able and willing to comply with study visits and procedures as per

- Patient should understand, sign, and date the written voluntary informed consent form
at the screening visit prior to any protocol-specific procedures performed.

- Patients must be covered by a medical insurance

Exclusion Criteria:

- Patient having received previous treatment with PI3K and/or mTOR inhibitors

- Patient with symptomatic CNS metastases NB: Patients with controlled and asymptomatic
CNS metastases may participate in this trial. As such, the patient must have
completed any prior treatment for CNS metastases > 28 days (including radiotherapy
and/or surgery) prior to enrollment in this study and should not be receiving chronic
corticosteroid therapy for the CNS metastases.

- 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)

- Patient has any of the following mood disorders as judged by the Investigator or a

- 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)

- ≥ CTCAE grade 3 anxiety

- or 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 concurrently using other approved or investigational anti-neoplastic agent

- Patient who has received wide field radiotherapy ≤ 4 weeks or limited field radiation
for palliation ≤ 2 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

- Patient having had major surgery within 14 days prior to starting study drug or has
not recovered from major side effects of the surgery

- Patient with poorly controlled diabetes mellitus (i.e. HbA1c > 8 %)

- 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)

- QTc > 480 (female) or 470 msec (male) on screening ECG (using the QTcF formulae)

- Angina pectoris that requires the use of anti-anginal medication

- Ventricular arrhythmias except for benign premature ventricular contractions

- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled
with medication

- Conduction abnormality requiring a pacemaker

- Valvular disease with documented compromise in cardiac function

- Symptomatic pericarditis

- 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

- 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

- Patient with impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

- 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

- Patient has other concurrent severe and/or uncontrolled medical condition that would,
in the investigator's judgment contraindicate her participation in the clinical study
(e.g.,chronic pancreatitis, active chronic hepatitis etc.)

- Patient has a history of non-compliance to medical regimen

- Patient is currently being treated with drugs known to be moderate and strong
inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
or switched to a different medication prior to starting study drug.

- Patient has a known history of HIV infection

- Pregnant or nursing (lactating) woman

- Patient has a known hypersensitivity to any of the excipients of BKM120

- Patient has not recovered to grade 1 or better (except alopecia) from related side
effects of any prior antineoplastic therapy

- Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for
treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight
heparin (LMWH), or fondaparinux is allowed

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

2 months disease control rate

Outcome Description:

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

Outcome Time Frame:

2 months after the first BKM120 intake

Safety Issue:


Principal Investigator


Investigator Role:

Principal Investigator

Investigator Affiliation:

Centre Léon Bérard, Lyon- FRANCE


France: Agence Nationale de Sécurité du Médicament et des produits de santé

Study ID:




Start Date:

January 2013

Completion Date:

July 2015

Related Keywords:

  • Head and Neck Neoplasms
  • Neoplasm Metastasis
  • Recurrent Disease
  • Progressive Disease
  • Metastatic head and neck cancer
  • PI3K inhibitor
  • Recurrent head and meck cancer
  • Progressive head and neck cancer
  • BKM120
  • Neoplasms
  • Head and Neck Neoplasms
  • Neoplasm Metastasis