The goal of the Phase I portion of this study is to find the highest tolerable dose of the combination of dasatinib and erlotinib hydrochloride that can be given to patients with advanced solid tumors.

The goal of the Phase II portion of this study is to learn if this combination is effective when given to patients with non-small cell lung cancer.

The safety of this combination will be studied in both phases.

The Study Drugs:

Dasatinib is designed to decrease the activity of one or more proteins that are responsible for the uncontrolled growth of tumor cells. This may cause the tumor cells to die.

Erlotinib hydrochloride is designed to block the activity of a protein found on the surface of many tumor cells. Blocking the protein may control tumor growth and survival. This may stop tumors from growing.

Study Groups:

If you are found to be eligible to participate in this study, you will be assigned to a study group based on when you joined this study. Up to 6 groups of 3-6 participants each will be enrolled in the Phase I portion of the study, and up to 35 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of dasatinib you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of dasatinib. Each new group will receive a higher dose of dasatinib than the group before it, if no intolerable side effects were seen. If intolerable side effects are seen, the next group of participants may receive the same dose level or a lower dose level. This will continue until the highest tolerable dose of dasatinib is found.

If you are enrolled in the Phase II portion, you will receive highest tolerated dose level of dasatinib that was found in the Phase I portion.

All participants will receive the same dose level of erlotinib hydrochloride. If the doctor thinks it is needed, the dose level may be lowered.

Study Drug Administration:

If you are in Phase I, on Day -3 of Cycle 1 (3 days before your first dose of study drugs), you will take erlotinib hydrochloride by mouth. On Days 1-19 of Cycle 1, you will be take dasatinib and erlotinib hydrochloride by mouth once a day. On Days 20 and 21 of Cycle 1, you will only take dasatinib by mouth once a day. Every day of Cycles 2 and beyond, you will take dasatinib and erlotinib hydrochloride by mouth once a day.

If you are in Phase II, every day you will take dasatinib and erlotinib hydrochloride by mouth once a day.

Each cycle is 21 days.

Erlotinib hydrochloride and dasatinib should be taken together at the same time every day. The tablets must be swallowed whole and may not be broken. The tablets should be taken with 1 cup (about 8 ounces) of water. Dasatinib and erlotinib hydrochloride should be taken 1 hour before or 2 hours after meals or any other drugs, and should not be taken with grapefruit juice. The entire dose must be taken at 1 time. If you vomit within 30 minutes of swallowing the tablets, the dose may be replaced if the tablets can be seen and counted. If you are currently taking St. John's Wort, you should stopping taking if for at least 5 days before taking dasatinib.

Study Visits:

At Week 1 of Cycle 1, your vital signs and weight will be measured.

At the end of Week 3 of every cycle, the following tests and procedures will be performed:

• You will have a physical exam, including measurement of your vital signs and weight.
• You will have a performance status evaluation.
• Blood (about 1 tablespoon) will be drawn for routine tests
• The amount of oxygen in your blood will be measured by a pulse oximeter.
• You will have a chest x-ray to check the status of the disease.
• You will be asked if you have experienced any side effects and to list any drugs you may be taking.
• Women who are able to become pregnant must have a negative blood (about 1-2 teaspoons) or urine pregnancy test.

At the end of Week 3 of Cycles 1 and 3, you will also have an ECG.

At the end of Week 3 of every other cycle (Cycles 2, 4, 6, and so on), you will also have a chest CT scan or a whole body PET/CT (if necessary) to check the status of the disease.

Phase I PK Testing:

If you are in Phase I, you will have blood (about 2 teaspoons each time) drawn for PK testing.

• On Day -3 of Cycle 1, blood will be drawn 5 different times.
• On Days -2, -1, and 1 of Cycle 1, blood will be drawn 1 time.
• On Day 19 of Cycle 1, blood will be drawn 5 times.
• On Days 20, 21, and 22 of Cycle 1, blood will be drawn 1 time.

Length of Study:

You may stay on study for as long as you are benefitting. You will be taken off study if you experience intolerable side effects or the disease gets worse.

End-of-Study Visit:

At the end of your study participation, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

• You will have a physical exam, including measurement of your vital signs and weight.
• You will have a performance status evaluation.
• Blood (about 1 tablespoon) will be drawn for routine tests.
• The amount of oxygen in your blood will be measured.
• You will have a chest x-ray to check the status of the disease.
• You will have an ECG.

If you are taken off study due to unacceptable side effects, you will be called and asked about any side effects until the side effect gets better or becomes stable.

Long-Term Follow-Up:

After the end-of-study visit, you will be contacted every 3-4 months for 1 year to collect information about how you are doing. You (or your family members or designees) may be contacted by telephone or during clinic visits. If you are called, this will take about 5 minutes.

This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of acute lymphoid and chronic myeloid leukemia. Erlotinib hydrochloride is FDA approved and commercially available for the treatment of non-small cell lung cancer. The use of this combination in this study is investigational.

Up to 59 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Advanced malignancy that is appropriate for systemic therapy without curative intent.
2. Patients must provide verbal and written informed consent indicating they are aware of the investigational nature of the study. Parental consent and patient assent is required for those aged 16-17.
3. Patients must be at least 16 years of age.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
5. Adequate hematologic, hepatic, and renal function as follows: creatinine < 1.5 x the institutional upper limit of normal (ULN), total bilirubin < 2.0 x ULN, AST and ALT < 2.5 x ULN, absolute granulocytes >/= 1500/mm^3; platelets >/= 75,000 mm^3; hemoglobin >/= 10 g/dL.
6. Serum potassium, magnesium, and phosphate within the institutional limits of normal. Patients with low potassium, phosphate, or magnesium levels may be repleted to allow for protocol entry.
7. Serum calcium >/= the institutional limits of normal. Patients with low calcium levels may be repleted to allow for protocol entry.
8. Ability to take oral medication (dasatinib and erlotinib must be swallowed whole)
9. Patients-both males & females-w/reproductive potential must agree to use an adequate method of contraception to include hormonal contraceptives (birth control pills, injections, implants), intrauterine device (IUD), barrier contraceptive with spermicide, and/or abstinence throughout the study & for at least 4 wks after the study drugs are stopped. Females w/ reproductive or childbearing potential include any female who has experienced menarche & who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal
10. -Continued from Inclusion #9 - [defined as amenorrhea >/=12 consecutive mths;or women on hormone replacement therapy (HRT) w/ documented serum follicle stimulating hormone (FSH) level > 35 milli-International unit (mIU)/mL]. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
11. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 72 hours prior to the start of study drug administration.
12. Asymptomatic brain metastases with prior cranial irradiation or resection are acceptable if there is no bleeding, no midline shift, and no need for steroids or anti-convulsants. Asymptomatic brain metastasis without prior treatment are acceptable if the largest lesion is less than 7 mm in diameter, there is no bleeding, midline shift, nor need for steroids or anti-convulsants.
13. Patient agrees to discontinue St. Johns Wort at least 5 days before starting dasatinib or erlotinib.
14. Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
15. The patient's O^2 saturation must be >92% on room air.
16. (Phase II only) - Patient has never received prior therapy with dasatinib, or erlotinib, or another epidermal growth factor receptor (EGFR) or Src family kinase (SFK) inhibitor.
17. (Phase I only) - Histological or unequivocal cytological proof of solid tumor malignancy.
18. (Phase I only) - At least one prior systemic chemotherapy or biological therapy for recurrent or metastatic solid tumor (i.e., this protocol therapy must be administered as second line or greater), ), except if there is no standard or experimental systemic therapy available. If no effective systemic agent is available for first line therapy, then patients may be enrolled on the phase I as first line therapy.
19. (Phase I only) - Prior radiotherapy is permitted (see exclusion criterion 4 for details on unallowable radiotherapy).
20. (Phase II only) - Histological or unequivocal cytological proof of NSCLC.
21. (Phase II only) - NSCLC that is appropriate for systemic therapy without curative intent: Stage IV, Stage IIIB with pleural effusion, or incurable recurrent disease after surgery or radiotherapy.
22. (Phase II only) - Zero to one line of prior systemic therapy for recurrent or metastatic NSCLC. Prior adjuvant chemotherapy or adjuvant biologic therapy for NSCLC is not included as a line of prior therapy if it was completed greater than 3 months prior to recurrence, provided that the patient has never received any EGFR or SFK inhibitors.
23. (Phase II only) - Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
24. (Phase II only) - Availability of tumor tissue that is at least adequate for EGFR mutational analysis. This can come from pre-existing paraffin blocks (from diagnostic biopsy or surgical resection) or patient may undergo a biopsy for research purposes.
25. (Phase II only) - Prior radiotherapy is permitted as long as there is measurable disease outside of the radiotherapy port OR clearly recurrent and growing within the radiotherapy port (see exclusion criterion 2 for details on unallowable radiotherapy).

Exclusion Criteria:

1. Women who are pregnant, breastfeeding, or have child-bearing potential and are unwilling/unable to use an acceptable method of contraception for the entire study period and for at least 4 weeks after cessation of the study drugs. All women of child-bearing potential must have a negative pregnancy test prior to first receiving protocol therapy. If the pregnancy test is positive, the patient must not receive dasatinib or erlotinib, and must not be enrolled on the study
2. Radiotherapy to ribs, sternum, pelvis, vertebrae or skull within 4 weeks prior to entering the study. (If none of these axial skeletal areas are included in the radiotherapy field, patients may have received palliative radiotherapy to long bones provided that it has ended at least 2 weeks prior to initiation of dasatinib-erlotinib therapy.)
3. Patients with any of the following cardiac problems should be excluded: (a) Uncontrolled angina, congestive heart failure, or myocardial infarction within the previous 6 months; (b) Diagnosed congenital long QT syndrome; (c) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); (d) Prolonged [1] corrected QT interval (QTc) interval on pre-entry electrocardiogram (> 450 msec in women or >440 msec in men). If the automated reading is prolonged, the ECG should be manually over read.
4. Continued from Exclusion #4: (e) Any history of second or third degree heart block unless they currently have a pacemaker; (f) Heart rate < 50 / minute on pre-entry electrocardiogram;(g) Uncontrolled hypertension defined as systolic blood pressure > 150 or diastolic >100;(h) Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.
5. Patients with pericardial effusion > grade 1 (by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0).
6. Patients with pleural effusion > grade 2 (by CTCAE v3.0). A grade 3 pleural effusion that is managed by a thoracentesis or an indwelling catheter is allowable as long as supplemental oxygen is not required.
7. Patients with any condition that impairs their ability to swallow, retain, or absorb dasatinib or erlotinib tablets are excluded. This includes any condition resulting in an inability to take oral medication, a requirement for IV alimentation, prior surgical procedures that have resulted in chronic malabsorption, or active peptic ulcer disease.
8. Patients with > grade 2 neuropathy
9. Patients with a history of pulmonary fibrosis (other than in a radiated field).
10. Patients with inflammatory bowel disease or uncontrolled chronic diarrhea.
11. Patients with a history of significant bleeding disorder unrelated to cancer, including: (a) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease); (b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); (c) Ongoing or recent (\

Adverse event collection was through each 3 week treatment cycle, up to 12 weeks of assessment with treatment.