PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
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
2 other identifiers
interventional
12
1 country
1
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2013
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 20, 2013
CompletedFirst Posted
Study publicly available on registry
March 22, 2013
CompletedStudy Start
First participant enrolled
May 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2020
CompletedResults Posted
Study results publicly available
October 27, 2020
CompletedOctober 5, 2021
September 1, 2021
4.9 years
March 20, 2013
September 16, 2020
September 14, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
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.
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
28 days
Secondary Outcomes (6)
Apoptosis Induction
Up to 28 days
Response Rate Assessed Using RECIST
Up to 28 days
Response Rate in Patients With Prior EGFR Failure Assessed Using RECIST
Up to 28 days
Tumor Shrinkage
Up to 28 days
Overall Survival
4 years and 3 months
- +1 more secondary outcomes
Study Arms (1)
Arm I (BKM120 PO and cetuximab 500 mg IV 14 days)
EXPERIMENTALPatients 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.
Interventions
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- 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
- 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)
- +8 more criteria
You may not qualify if:
- 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
- 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
- +28 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Chicagolead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr Everett Vokes, MD
- Organization
- University of Chicago Medicine and Biological Sciences
Study Officials
- PRINCIPAL INVESTIGATOR
Tanguy Seiwert
University of Chicago Comprehensive Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 20, 2013
First Posted
March 22, 2013
Study Start
May 1, 2013
Primary Completion
April 1, 2018
Study Completion
September 1, 2020
Last Updated
October 5, 2021
Results First Posted
October 27, 2020
Record last verified: 2021-09