Recruitment

Recruitment Status
Completed
Estimated Enrollment
30

Inclusion Criteria

Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential
Presence of measurable lesions (RECIST V1.1)
International normalized ratio (INR) =< 2.5
...
Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential
Presence of measurable lesions (RECIST V1.1)
International normalized ratio (INR) =< 2.5
Serum amylase =< ULN
Patients must have at least one site of measurable disease (if applicable) (per RECIST for solid tumors or the appropriate disease classification/criteria for the target population)
Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome)
Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 1.5 x normal range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
Prior use of cetuximab or another epidermal growth factor receptor (EGFR) inhibitor is allowable and if used as a single agent should not be considered as a cytotoxic chemotherapy
Mandatory tumor biopsy/biopsies in accessible tumors; for inaccessible tumors availability of tissue is required: >= 10 tumor containing formalin-fixed paraffin-embedded (FFPE) slides/sections
Signed informed consent
Magnesium >= the lower limit of normal for the institution
Potassium within normal limits for the institution
Serum lipase =< ULN
Hemoglobin (Hb) > 9 g/dL
Total calcium (corrected for serum albumin) within normal limits
Histologically / cytologically confirmed diagnosis of squamous cell carcinoma of head and neck origin not amenable to curative intent therapy; both human papillomavirus (HPV)(+) and HPV(-) tumors are eligible; tumors (squamous histology) of unknown primary that are clearly related to the head and neck area are eligible
Progressive disease after exposure to a platinating agent (e.g. cisplatin or carboplatin) in a prior line of therapy, or documented intolerance to such an agent
Platelets >= 100 x 10^9/L
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
No more than two lines of prior cytotoxic chemotherapy in the recurrent/metastatic (palliative intent) treatment setting
Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)

Exclusion Criteria

History of clinically significant heart failure (previously assessed) with a left ventricular ejection fraction (LVEF) of < 50% as determined by multiple grated acquisition (MUGA) scan or echocardiogram (ECHO)
Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
More than two prior lines of cytotoxic chemotherapy in the recurrent/metastatic disease setting (palliative treatment intent)(excluding single agent use of an EGFR inhibitor)
...
History of clinically significant heart failure (previously assessed) with a left ventricular ejection fraction (LVEF) of < 50% as determined by multiple grated acquisition (MUGA) scan or echocardiogram (ECHO)
Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
More than two prior lines of cytotoxic chemotherapy in the recurrent/metastatic disease setting (palliative treatment intent)(excluding single agent use of an EGFR inhibitor)
Patients who are currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant
Corrected QT (QTc) > 480 msec on screening electrocardiogram (ECG) (using the Fridericia QT correction [QTcF] formula)
Meets the cut-off score of >= 10 in the Patient Health Questionnaire 9 (PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder 7 (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
Documented cardiomyopathy
Women who are pregnant or breast-feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72 hours prior to initiating treatment
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 diarrhea >= CTCAE v4 grade 2
Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy; typically a >= 2 week interval since completion of prior therapy is recommended and 4 weeks for monoclonal antibodies
Angina pectoris that requires the use of anti-anginal medication
Known diagnosis of human immunodeficiency virus (HIV) infection unless patient is fully immunocompetent (cluster of differentiation 4 [CD4] > 200) and patient is not taking antiretroviral therapy
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); patients with unresolved diarrhea will be excluded as previously indicated
Patients who have received wide field radiotherapy =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
Patients with acute or chronic liver, renal disease or pancreatitis
Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLCO), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Patients with any history of hyperglycemia (elevated blood glucose level on blood chemistries) should be considered for initiation of Metformin treatment (500mg, PO, twice daily) prior to starting BKM120
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 stable low dose corticosteroids treatment (eg. dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible
Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
Patients with untreated brain metastases are excluded; however, patients with treated brain metastases are eligible if they are > 4 weeks from therapy completion (including radiation and/or surgery), are clinically stable at the time of study entry and are not receiving corticosteroid therapy at the time of study entry
>= Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4) grade 3 anxiety
No available tumor material for correlative studies
Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial
History of documented congestive heart failure (New York Heart Association functional classification III-IV)
Ventricular arrhythmias except for benign premature ventricular contractions
Conduction abnormality requiring a pacemaker
Patients who have undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
Patients with a known hypersensitivity to BKM120 or to its excipients, or hypersensitivity to cetuximab
History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix, or any tumor that is after clearing with the principal investigator (PI) clearly not considered to have impact on prognosis
Symptomatic pericarditis
Patients who are currently 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
Patients who have received prior treatment with a P13K inhibitor
Patient has poorly controlled diabetes mellitus or steroid-induced diabetes mellitus (hemoglobin A1C [HbA1C] > 7.5%)
Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function
Valvular disease with document compromise in cardiac function
Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3, subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits
Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug

Summary

Conditions
  • Recurrent Metastatic Squamous Neck Cancer With Occult Primary
  • Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
  • Stage IVC Squamous Cell Carcinoma of the Larynx
  • Stage IVB Salivary Gland Cancer
  • Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Squamous Cell Carcinoma of the Oropharynx
  • Stage IVA Squamous Cell Carcinoma of the Oropharynx
  • Stage IVA Verrucous Carcinoma of the Oral Cavity
  • Stage IVB Squamous Cell Carcinoma of the Larynx
  • Stage IVC Squamous Cell Carcinoma of the Oropharynx
  • Recurrent Salivary Gland Cancer
  • Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVB Verrucous Carcinoma of the Larynx
  • Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Squamous Cell Carcinoma of the Hypopharynx
  • Recurrent Squamous Cell Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Nasopharynx
  • Salivary Gland Squamous Cell Carcinoma
  • Stage IVA Squamous Cell Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Oropharynx
  • Stage IVB Verrucous Carcinoma of the Oral Cavity
  • Stage IVC Verrucous Carcinoma of the Oral Cavity
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Stage IVC Verrucous Carcinoma of the Larynx
  • Stage IVA Verrucous Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Recurrent Verrucous Carcinoma of the Larynx
  • Stage IVA Salivary Gland Cancer
  • Stage IVC Salivary Gland Cancer
  • Recurrent Verrucous Carcinoma of the Oral Cavity
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Tongue Cancer
Type
Interventional
Phase
Phase 1Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

PRIMARY OBJECTIVES: I. Induction of compensatory signaling/feedback loop signaling after one week of BKM120 (PI3K inhibitor BKM120) (run-in) compared to patients not treated with BKM120. II. Safety and tolerability of combined treatment with BKM120 and cetuximab. SECONDARY OBJECTIVES: I. Induction o...

PRIMARY OBJECTIVES: I. Induction of compensatory signaling/feedback loop signaling after one week of BKM120 (PI3K inhibitor BKM120) (run-in) compared to patients not treated with BKM120. II. Safety and tolerability of combined treatment with BKM120 and cetuximab. SECONDARY OBJECTIVES: I. Induction of apoptosis after one week of BKM120 (run-in) compared to patients not treated with BKM. II. Tumor shrinkage (based Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 [V1.1] measurements) in patients treated with combination. III. Response rate (based RECIST V1.1 measurements) in patients treated with combination. IV. Overall survival. V. Progression free survival. OUTLINE: This is a phase I, dose-escalation study of PI3K inhibitor BKM120, followed by a phase II study. RUN-IN-PERIOD: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive PI3K inhibitor BKM120 orally (PO) once daily (QD) on days -7 to 0. Patients complete 1 week washout before dose escalation. ARM II: Patients receive no treatment on days -7 to 0. All patients receive PI3K inhibitor BKM120 PO QD on days 1-28 and cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 28 days.

Inclusion Criteria

Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential
Presence of measurable lesions (RECIST V1.1)
International normalized ratio (INR) =< 2.5
...
Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential
Presence of measurable lesions (RECIST V1.1)
International normalized ratio (INR) =< 2.5
Serum amylase =< ULN
Patients must have at least one site of measurable disease (if applicable) (per RECIST for solid tumors or the appropriate disease classification/criteria for the target population)
Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome)
Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 1.5 x normal range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present)
Prior use of cetuximab or another epidermal growth factor receptor (EGFR) inhibitor is allowable and if used as a single agent should not be considered as a cytotoxic chemotherapy
Mandatory tumor biopsy/biopsies in accessible tumors; for inaccessible tumors availability of tissue is required: >= 10 tumor containing formalin-fixed paraffin-embedded (FFPE) slides/sections
Signed informed consent
Magnesium >= the lower limit of normal for the institution
Potassium within normal limits for the institution
Serum lipase =< ULN
Hemoglobin (Hb) > 9 g/dL
Total calcium (corrected for serum albumin) within normal limits
Histologically / cytologically confirmed diagnosis of squamous cell carcinoma of head and neck origin not amenable to curative intent therapy; both human papillomavirus (HPV)(+) and HPV(-) tumors are eligible; tumors (squamous histology) of unknown primary that are clearly related to the head and neck area are eligible
Progressive disease after exposure to a platinating agent (e.g. cisplatin or carboplatin) in a prior line of therapy, or documented intolerance to such an agent
Platelets >= 100 x 10^9/L
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
No more than two lines of prior cytotoxic chemotherapy in the recurrent/metastatic (palliative intent) treatment setting
Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)

Exclusion Criteria

History of clinically significant heart failure (previously assessed) with a left ventricular ejection fraction (LVEF) of < 50% as determined by multiple grated acquisition (MUGA) scan or echocardiogram (ECHO)
Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
More than two prior lines of cytotoxic chemotherapy in the recurrent/metastatic disease setting (palliative treatment intent)(excluding single agent use of an EGFR inhibitor)
...
History of clinically significant heart failure (previously assessed) with a left ventricular ejection fraction (LVEF) of < 50% as determined by multiple grated acquisition (MUGA) scan or echocardiogram (ECHO)
Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
More than two prior lines of cytotoxic chemotherapy in the recurrent/metastatic disease setting (palliative treatment intent)(excluding single agent use of an EGFR inhibitor)
Patients who are currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant
Corrected QT (QTc) > 480 msec on screening electrocardiogram (ECG) (using the Fridericia QT correction [QTcF] formula)
Meets the cut-off score of >= 10 in the Patient Health Questionnaire 9 (PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder 7 (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
Documented cardiomyopathy
Women who are pregnant or breast-feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 72 hours prior to initiating treatment
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 diarrhea >= CTCAE v4 grade 2
Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy; typically a >= 2 week interval since completion of prior therapy is recommended and 4 weeks for monoclonal antibodies
Angina pectoris that requires the use of anti-anginal medication
Known diagnosis of human immunodeficiency virus (HIV) infection unless patient is fully immunocompetent (cluster of differentiation 4 [CD4] > 200) and patient is not taking antiretroviral therapy
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); patients with unresolved diarrhea will be excluded as previously indicated
Patients who have received wide field radiotherapy =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
Patients with acute or chronic liver, renal disease or pancreatitis
Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLCO), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Patients with any history of hyperglycemia (elevated blood glucose level on blood chemistries) should be considered for initiation of Metformin treatment (500mg, PO, twice daily) prior to starting BKM120
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 stable low dose corticosteroids treatment (eg. dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible
Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
Patients with untreated brain metastases are excluded; however, patients with treated brain metastases are eligible if they are > 4 weeks from therapy completion (including radiation and/or surgery), are clinically stable at the time of study entry and are not receiving corticosteroid therapy at the time of study entry
>= Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4) grade 3 anxiety
No available tumor material for correlative studies
Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial
History of documented congestive heart failure (New York Heart Association functional classification III-IV)
Ventricular arrhythmias except for benign premature ventricular contractions
Conduction abnormality requiring a pacemaker
Patients who have undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
Patients with a known hypersensitivity to BKM120 or to its excipients, or hypersensitivity to cetuximab
History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix, or any tumor that is after clearing with the principal investigator (PI) clearly not considered to have impact on prognosis
Symptomatic pericarditis
Patients who are currently 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
Patients who have received prior treatment with a P13K inhibitor
Patient has poorly controlled diabetes mellitus or steroid-induced diabetes mellitus (hemoglobin A1C [HbA1C] > 7.5%)
Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function
Valvular disease with document compromise in cardiac function
Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3, subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits
Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug

Tracking Information

NCT #
NCT01816984
Collaborators
National Cancer Institute (NCI)
Investigators
  • Principal Investigator: Tanguy Seiwert University of Chicago Comprehensive Cancer Center
  • Tanguy Seiwert University of Chicago Comprehensive Cancer Center