A Phase I Study of Nilontinib and Cetuximab in Patients With Solid Tumors

ABL1 has been suggested to play a key role in the resistance mechanism to anti EGFR therapy
in cancer. Therefore, this study aims to evaluate the safety and possible effect of targeting
both EGFR using cetuximab along with ABL1 using nilotinib. Correlative studies assess the
changes in tumor proteome in response to therapy and magnitude of ADCC as a marker of
antibody activity.

Inclusion Criteria:

1. Recurrent and/or metastatic Kras wildtype colorectal cancer or squamous cell carcinoma
of the head and neck

2. Previous therapy:

1. Patients must have progressed after standard therapy for metastatic/recurrent
disease, including irinotecan and oxaliplatin-containing regimens for patients
with CRC and platinum-containing regimens for patients with H&NSCC.

2. Patients may have received cetuximab or panitumumab previously

3. Ability to swallow medication tablets by mouth (which may include taking nilotinib
mixed in apple sauce)

4. At least one measurable lesion by RECIST criteria

5. A tumor lesion that can be readily biopsied using a core needle via clinical exam or
image-guidance.

6. Over the age of 18 years and able to provide informed consent

7. Adequate kidney, liver, and bone marrow function as follows:

1. Hemoglobin >/= 8.0 gm/dL

2. Absolute neutrophil count >/= 1500

3. Platelet count >/= 100,000

4. Creatinine within institutional normal limits or glomerular filtration rate > 60

5. Total bilirubin f. AST and ALT

8. Life expectancy of greater than 3 months

9. ECOG performance status

10. Normal left ventricular ejection fraction, defined as EF > 50%

Exclusion Criteria:

1. Chemotherapy or surgery within 4 weeks prior to treatment start

2. Radiation treatment within 3 weeks prior to treatment start

3. Prior therapy with nilotinib, ponatinib, dasatinib, or imatinib

4. Untreated brain metastases or neurologically unstable central nervous system
metastases; CNS metastases will be considered stable if there is no new nor enlarging
lesions for one month, and the patient remains off steroids and anti-epileptics for
the same time period

5. Any severe or uncontrolled medical condition or other condition that could affect
participation in this study, including: unstable angina, uncontrolled hypertension,
serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial
infarction

6. Diarrhea > Grade 1 at baseline

7. Concomitant medication or herbal therapy known to inhibit CYP3A4

8. Gastrointestinal tract disease resulting in the inability to take oral medication or a
requirement for IV alimentation, prior surgical procedures affecting absorption, or
active peptic ulcer disease

9. Ongoing ventricular cardiac dysrhythmias of NCI CTCAE grade >/= 2

10. Subjects with a history of serious ventricular arrhythmia (ventricular tachycardia or
ventricular fibrillation >/= 3 beats in a row)

11. Serious cardiac arrhythmia requiring medication

12. QTc interval > 500 msec

13. Female patients who are pregnant or breast feeding, or adults who are of reproductive
potential and are unwilling to refrain from conceiving a child during study treatment

14. Patients unwilling or unable to comply with the protocol, or provide informed consent