Inclusion Criteria:

- histologically or cytologically confirmed advanced or metastatic head and neck
squamous cell (HNSCC) cancer not amenable to potentially curative resection.

- Tumor must be amenable to sequential biopsies, and patients must be willing to
undergo 3 sequential tumor biopsies.

- evidence of progression after first-line chemotherapy for locally advanced or
recurrent disease. There has to be at least a 4-week period since the last
administration of prior therapy and initiation of the current study drugs.

- Cetuximab is indicated. However, prior therapy with cetuximab (particularly if in the
primary setting) is allowed.

- Presence of measurable target on a CT-scan available for external review, with at
least one diameter >/= 2cm (>/= 1cm if spiral CT-scan is used for assessment and
follow-up).

- Age >/= 18 years.

- The Eastern Cooperative Oncology Group (ECOG) performance status <2 (Karnofsky >60%,
see Appendix A).

- Life expectancy greater than 12 weeks.

- Patients must have normal organ and marrow function as defined below:

- leukocytes >3,000/μl

- absolute neutrophil count >1,500/μl

- platelets >100,000/μl

- total bilirubin <1.5x Upper limit normal (ULN)

- Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) <2.5 X institutional
upper limit of normal

- creatinine <1.5x ULN OR

- creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine above ULN.

- All women of child-bearing potential (WCBP),all sexually active male patients, and
all partners of patients must agree to use adequate methods of birth control
throughout the study. Women of child-bearing potential (defined as being less than 1
year post-menopausal) must have a negative serum or urine β human chorionic
gonadotropin (βhCG) pregnancy test; and men and women of reproductive potential must
agree to practice an effective method of avoiding pregnancy while receiving study
drug and for 30 days after the final dose of study drug.

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
the study or those who have not recovered from adverse events due to agents
administered more than 4 weeks earlier.

- Patients receiving any other investigational agents.

- Patients with known brain metastases.

- History of allergic reactions attributed to cetuximab or compounds of similar
chemical or biologic composition to IPI-926.

- Patients taking rifampin, St. John's wort, carbamazepine, phenytoin, and
phenobarbital are excluded from this trial.

- Uncontrolled illness including, hypertension, ongoing or active infection, bleeding
diathesis, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Baseline Fridericia's formula (QTcF) >450 msec in men or >470 msec in women.

- Concurrent treatment with any agent known to prolong the Corrected QT (QTc) interval

- Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep
vein thrombosis) requiring anticoagulation and meet any of the following criteria are
excluded:

- Have been on a stable dose of anticoagulation for <1 month

- Have had a Grade 2, 3 or 4 hemorrhage in the past month

- Are experiencing continued symptoms from their venous thromboembolic event
Patients who have had a venous thromboembolic event but do not meet any of the
above three criteria are eligible for participation.

- History of a seizure within the last 10 years or seizure disorder requiring
anti-epileptic medications.

- Known HIV-positive patients.

- Therefore, patients taking potent inhibitors or inducers of Cytochrome P450 3A4 (CYP
3A4) should not be enrolled on this study.

- active infection or systemic use of antibiotic within 72 hours of treatment

- Cirrhotic liver disease, ongoing alcohol abuse, or chronic active or acute hepatitis