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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

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

Detailed Summary:

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 s
Sponsor: University of Chicago

Current Primary Outcome:

  • Compensatory signaling/feedback loop signaling evaluated by measurement of phosphorylated (p)-EGFR [ Time Frame: 1 week ]
    Performed using snap frozen tissue samples using the well-established PamGene Kinase array platform available in the Salgia/Seiwert laboratories.
  • Maximum tolerated dose (MTD) 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 [ Time Frame: 28 days ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Apoptosis induction [ Time Frame: Up to 28 days ]
    Measured by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on Formalin-Fixed, Paraffin-Embedded (FFPE) sections in a descriptive manner.
  • Response rate assessed using RECIST [ Time Frame: Up to 28 days ]
  • Response rate in patients with prior EGFR failure assessed using RECIST [ Time Frame: Up to 28 days ]
  • Tumor shrinkage [ Time Frame: Up to 28 days ]
    Tumor shrinkage will be visualized as a waterfall plot for graphical (qualitative) comparison.
  • Overall survival [ Time Frame: Up to 28 days ]
    Kaplan-Meier curves will be generated. Logistic and Cox proportional hazards regression models will also be used.
  • Progression free survival [ Time Frame: Up to 28 days ]
    Kaplan-Meier curves will be generated. Logistic and Cox proportional hazards regression models will also be used.


Original Secondary Outcome: Same as current

Information By: University of Chicago

Dates:
Date Received: March 20, 2013
Date Started: May 2013
Date Completion: June 2017
Last Updated: January 9, 2017
Last Verified: January 2017