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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Centre Leon Berard
Sponsor:
Collaborators:
National Cancer Institute, France
Fondation ARC
Information provided by (Responsible Party):
Centre Leon Berard
ClinicalTrials.gov Identifier:
NCT01737450
First received: November 13, 2012
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

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 patin and cetuximab-based chemotherapy.


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:
  • 2 months disease control rate [ Time Frame: 2 months after the first BKM120 intake ] [ Designated as safety issue: No ]
    Control rate= Complete response, partial response and stable disease according to RECIST 1.1


Secondary Outcome Measures:
  • Progression free survival [ Time Frame: At 2 months, 4 months and then every 2 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Baseline, at 2 months, 4 months and then every 2 months at the end of Study ] [ Designated as safety issue: No ]
    OS will be measured from the date of inclusion to the date of death from any cause.

  • Safety [ Time Frame: continuous up to 30 days after the last treatment ] [ Designated as safety issue: No ]
    The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTC-AE V4.0) grade.

  • Objective response rate [ Time Frame: At Baseline, 2 months, 4 months and then every 2 months, at the end of Study ] [ Designated as safety issue: No ]
    Objective response rate is defined as the proportion of patient with complete or partial response according RECIST 1.1

  • Duration of response [ Time Frame: At Baseline, 2 months, 4months and then every 2 months, at the end of Study ] [ Designated as safety issue: No ]
    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.

  • Time to Progression [ Time Frame: At Baseline, 2 months, 4months and then every 2 months, at the end of Study ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 70
Study Start Date: January 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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) at time of study drug start
  • Documented mutational status of PIK3CA before study drug start (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 protocol.
  • 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 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 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 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 alopecia).
    • 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 eligible.
    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01737450

Contacts
Contact: Jérôme FAYETTE, MD jerome.fayette@lyon.unicancer.fr

Locations
France
Hopital St André Recruiting
Bordeaux, France
Contact: Alain Ravaud    05 56 79 58 08    alain.ravaud@chu-bordeaux.fr   
Principal Investigator: Alain RAVAUD         
Sub-Investigator: Laurence DIGUE         
Hôpital BEAUJON Not yet recruiting
Clichy, France
Contact: Sandrine FAIVRE, MD       sandrine.faivre@bjn.aphp.fr   
Principal Investigator: Sandrine FAIVRE, MD         
Centre Oscar Lambret Recruiting
Lille, France
Contact: Audrey MAILLIEZ, MD    +33 3 20 29 59 43    a-mailliez@o-lambret.fr   
Contact: Gautier LEFEBVRE    +33 3 20 29 59 54    g-lefebvre@o-lambret.fr   
Principal Investigator: Audrey MAILLIEZ, MD         
Sub-Investigator: Gautier LEFEVBRE, MD         
Centre Léon Bérard Recruiting
Lyon, France
Contact: Jérome FAYETTE, MD       jerome.fayette@lyon.unicancer.fr   
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: Louis TASSY, MD         
Centre Val d'Aurelle - Paul Lamarque Recruiting
Montpellier, France
Contact: Didier CUPISSOL, MD       didier.cupissol@montpellier.unicancer.fr   
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       frederic.peyrade@nice.unicancer.fr   
Principal Investigator: Frédéric PEYRADE, MD         
Sub-Investigator: Christophe HEBERT, MD         
Sub-Investigator: Esma SAADA-BOUZID, MD         
Institut Curie Recruiting
Paris, France
Contact: Christophe LETOURNEAU, MD       christophe.letourneau@curie.net   
Principal Investigator: Christophe LE TOURNEAU, MD         
Sub-Investigator: Véronique DIERAS, MD         
Sub-Investigator: Marie-Paule SABLIN, MD         
Institut Gustave Roussy Recruiting
Villejuif, France
Contact: Caroline EVEN, MD    +33 1 42 11 46 17    caroline.even@gustaveroussy.fr   
Contact: François-Régis FERRAND, MD       francois-regis.ferrand@gustave.roussy.fr   
Principal Investigator: Caroline EVEN, MD         
Sub-Investigator: François-Régis FERRAND, MD         
Sub-Investigator: Margarida MATIAS, MD         
Sub-Investigator: Alfred SCHILF, MD         
Sponsors and Collaborators
Centre Leon Berard
National Cancer Institute, France
Fondation ARC
Investigators
Principal Investigator: Jérome FAYETTE, MD Centre Léon Bérard, Lyon- FRANCE
  More Information

Publications:
Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT01737450     History of Changes
Other Study ID Numbers: ET12-034, 2012-002403-18
Study First Received: November 13, 2012
Last Updated: July 9, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Centre Leon Berard:
Metastatic head and neck cancer
PI3K inhibitor
Recurrent head and meck cancer
Progressive head and neck cancer
BKM120

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

ClinicalTrials.gov processed this record on October 22, 2014