Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaPhase 1/2NCT01816984

PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

A Phase 1/2 study testing PI3K inhibitor BKM120 and cetuximab in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Recurrent Metastatic Squamous Neck Cancer With Occult Primary, run by University of Chicago at 1 site in United States.

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Salivary Gland Cancer
What is being tested?: PI3K inhibitor BKM120 and cetuximab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: May 2013to Sep 2020
Phase: Phase 1/2

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

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
Presence of measurable lesions (RECIST V1.1)
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
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
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
No more than two lines of prior cytotoxic chemotherapy in the recurrent/metastatic (palliative intent) treatment setting

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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
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)
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
Platelets >= 100 x 10^9/L
Hemoglobin (Hb) > 9 g/dL
Total calcium (corrected for serum albumin) within normal limits
Magnesium >= the lower limit of normal for the institution
Potassium within normal limits for the institution
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)
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
Serum amylase =< ULN
Serum lipase =< ULN
Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential
Signed informed consent
International normalized ratio (INR) =< 2.5

Who cannot join

Patients who have received prior treatment with a P13K inhibitor
No available tumor material for correlative studies
Patients with a known hypersensitivity to BKM120 or to its excipients, or hypersensitivity to cetuximab
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 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
Patients with acute or chronic liver, renal disease or pancreatitis

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Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire (treating physician to decide on whether to administer questionnaire):
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)
>= Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4) grade 3 anxiety
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)
Patients with diarrhea >= CTCAE v4 grade 2
Patient has active cardiac disease including any of the following:
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)
Corrected QT (QTc) > 480 msec on screening electrocardiogram (ECG) (using the Fridericia QT correction [QTcF] formula)
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 document compromise in cardiac function
Symptomatic pericarditis
Patient has a history of cardiac dysfunction including any of the following:
Myocardial infraction 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
Patient has poorly controlled diabetes mellitus or steroid-induced diabetes mellitus (hemoglobin A1C [HbA1C] > 7.5%)
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
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
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
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 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 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
Patients receiving chronic treatment with steroids or another immunosuppressive agent other than specified in exclusion criterion #4
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
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 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 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
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
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 who have undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
Patients who are currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant
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
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
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
Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470

Other trials in United States

About this study

Official title: A Biomarker Driven Pilot Study of the Pan-class I PI3K Inhibitor NVP-BKM120 in Combination With Cetuximab in Patients With Recurrent/Metastatic Head and Neck Cancer

This pilot randomized phase I/II trial studies the side effects and best dose of PI3K inhibitor BKM120 when given together with cetuximab and to see how well it works in treating patients with recurrent or metastatic head and neck cancer. PI3K inhibitor BKM120 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving PI3K inhibitor BKM120 together with cetuximab may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

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:

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.

Conditions: Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Salivary Gland Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Being tested: PI3K inhibitor BKM120, cetuximab
Medical subject headings: Salivary Gland Neoplasms, Squamous Cell Carcinoma of Head and Neck, Tongue Neoplasms

What participants receive

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

PI3K inhibitor BKM120Drug
Also called BKM120, PI3K_Inhibitor_BKM120
Given PO
cetuximabBiological
Also called C225, C225 monoclonal antibody, IMC-C225, MOAB C225
Given IV

Study groups in NCT01816984
Study group	Role	What they receive
Arm I (BKM120 PO and cetuximab 500 mg IV 14 days)	Experimental	Patients receive PI3K inhibitor BKM120 PO QD 100 mg/day on days -7 to 0. Patients complete 1 week washout. 3 patients receive BKM120 PO 80mg / day and cetuximab 500 mg IV /14 days and after dose escalation, 9 patients receive BKM120 PO 100mg / day and cetuximab 500 mg IV /14 days thereafter. All patients receive PI3K inhibitor BKM120 PO QD day on days 1-28 and cetuximab IV over 60-120 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: PI3K inhibitor BKM120; Biological: cetuximab

What is being measured

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

Compensatory Signaling/Feedback Loop Signaling Evaluated by Measurement of Phosphorylated (p)-EGFR
Performed using snap frozen tissue samples using the well-established PamGene Kinase array platform available in the Salgia/Seiwert laboratories.
Measured: 1 week
Maximum Tolerated Dose (MTD)
Maximum tolerated dose (MTD) is defined as the dose level preceding the dose in which greater than or equal to 2 out of 3-6 patients experience a dose limiting toxicity (DLT) assessed using CTCAE v4
Measured: 28 days

Secondary outcomes (6)

Apoptosis Induction
Measured by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on Formalin-Fixed, Paraffin-Embedded (FFPE) sections in a descriptive manner.
Measured: Up to 28 days
Response Rate Assessed Using RECIST
Percentage of patients whose cancer shrinks or disappears after treatment.
Measured: Up to 28 days
Response Rate in Patients With Prior EGFR Failure Assessed Using RECIST
Percentage of patients with prior EGFR failure assessed using RECIST whose cancer shrinks or disappears after treatment.
Measured: Up to 28 days
Tumor Shrinkage
Tumor shrinkage will be visualized as a waterfall plot for graphical (qualitative) comparison.
Measured: Up to 28 days
Overall Survival
Overall survival is defined as the time from study initiation to death due to any reason.
Measured: 4 years and 3 months
Progression Free Survival
Progression free survival is defined as the time from study initiation to first evidence of progression of disease.
Measured: 4 years and 3 months

Timeline

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

May 2013Sep 2020

First posted22 Mar 2013 (estimated)
Study startMay 2013
Primary completionApr 2018
Study completionSep 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaStudies of the same condition, open and under way.
More trials run by University of ChicagoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01816984
Sponsor's protocol ID: 12-1972
Other IDs: NCI-2013-00586
Status last verified: Sep 2021
First submitted: 20 Mar 2013
Last updated: 5 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No