Dasatinib and Erlotinib in Non-Small Cell Lung Cancer (NSCLC)

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00826449
• Collaborator: Bristol-Myers Squibb (Industry), OSI Pharmaceuticals (Industry)
• Enrollment: 53
• Location: 1
• Arm: 1
• Duration (Months): 63.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer; Non-Small Cell Lung Cancer	Drug: Dasatinib; Drug: Erlotinib	Phase 1/Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I-II Study of Dasatinib and Erlotinib in Non-Small Cell Lung Cancer
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase I Dasatinib + Erlotinib	Drug: Dasatinib; Starting dose of 70 mg by mouth daily for 21 day cycle.; Other Names: BMS-354825 Sprycel® ; Drug: Erlotinib; 150 mg by mouth daily every 21 day cycle.; Other Names: Erlotinib hydrochloride Tarceva OSI-774

Outcome Measures

Primary Outcome Measures

1. Phase I: Maximum Tolerable Dose (MTD) of Dasatinib Given With Erlotinib Hydrochloride [Baseline and at Day 21]

   MTD defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Dose-limiting toxicity (DLT) defined using NCI Common Terminology Common Terminology Criteria for Adverse Events (CTCAE) version 3 as: grade 3 or higher non-hematologic toxicity (excluding initial nausea and vomiting), grade 4 neutropenia, febrile neutropenia, or grade 4 thrombocytopenia. Grade 3-4 nausea and vomiting that cannot be controlled within 2 weeks with anti-emetics considered a DLT.

Secondary Outcome Measures

1. Phase II: Number of Participant With Response According to Response Evaluation Criteria in Solid Tumors (RECIST) [12 Weeks]

   Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Patients who have a partial or complete response or stable disease are defined as progression free. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): At least 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase.

2. Phase II: Progression-Free Survival (PFS) Rate [12 Weeks]

   A modified Thall, Simon, and Estey (1995) design used in the phase II study to monitor the proportion of patients with NSCLC who are alive and progression free (PFS) at twelve weeks after commencing treatment with dasatinib and erlotinib.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

2. Serum calcium >/= the institutional limits of normal. Patients with low calcium levels may be repleted to allow for protocol entry.

3. Ability to take oral medication (dasatinib and erlotinib must be swallowed whole)

4. 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

5. -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.

6. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 72 hours prior to the start of study drug administration.

7. 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.

8. Patient agrees to discontinue St. Johns Wort at least 5 days before starting dasatinib or erlotinib.

9. Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.

10. The patient's O^2 saturation must be >92% on room air.

11. (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.

12. (Phase I only) - Histological or unequivocal cytological proof of solid tumor malignancy.

13. (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.

14. (Phase I only) - Prior radiotherapy is permitted (see exclusion criterion 4 for details on unallowable radiotherapy).

15. (Phase II only) - Histological or unequivocal cytological proof of NSCLC.

16. (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.

17. (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.

18. (Phase II only) - Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

19. (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.

20. (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 (</= 3 months) significant gastrointestinal bleeding, defined as clinically evident hematemesis or hematochezia requiring therapeutic intervention.

12. Known HIV-positive patients are ineligible because of the potential for pharmacokinetic interactions between dasatinib and antiretroviral therapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.

13. Pts currently receiving any of the following medications will be excluded: (a) Any concurrent systemic anticancer therapy; (b) Any concurrent investigational agents (c) Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Pts must discontinue such drugs 7 days or more prior to starting dasatinib):i. quinidine, procainamide, disopyramide;ii. amiodarone, sotalol, ibutilide, dofetilide;iii. erythromycin, clarithromycin;iv. chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

14. Continued from Exclusion#14:v.cisapride,bepridil,droperidol,methadone,arsenic, chloroquine,domperidone,halofantrine,levomethadyl,pentamidine,sparfloxacin, lidoflazine;(d)The concomitant use of H2 blockers or proton pump inhibitors w/ dasatinib is not recommended.The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in pts receiving dasatinib therapy.If antacid therapy is needed,the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of dasatinib.

15. Continued from Exclusion #15: (e)Pt may not be receiving any prohibited CYP3A4 inhibitors Potent inhibitors of CYP3A4 are prohibited during study; for such medications, a wash-out period of 7 days is required prior to starting dasatinib. Potent CYP3A4 inhibitors include: · itraconazole, ketoconazole, miconazole, voriconazole; amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir; ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, imatinib, isoniazid, ketamine nefazodone, nicardipine, propofol, quinidine, telithromycin. (f) St.Johns Wort

16. The patient has received prior investigational therapy, chemotherapy, radiotherapy, or major surgery within 3 weeks of initiating study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Bristol-Myers Squibb
• OSI Pharmaceuticals

Investigators

• Principal Investigator: Faye M. Johnson, MD, PhD, BS, UT MD Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00826449
• Other Study ID Numbers: 2008-0353; NCI-2012-01653
• First Posted: Jan 22, 2009
• Last Update Posted: Jun 28, 2016
• Last Verified: May 1, 2016

• Keywords provided by M.D. Anderson Cancer Center: Advanced Solid Tumors; Advanced Cancer; Non-Small Cell Lung Cancer; NSCLC; Solid Tumor Malignancy; Dasatinib; BMS-354825; Sprycel®; Erlotinib; Erlotinib hydrochloride; Tarceva; OSI-774
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; Dasatinib

Study Results

Participant Flow

Recruitment Details	Recruitment Period: February 6, 2008 to July 18, 2012. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment Detail	Of the 53 participants registered, only 47 were eligible and treated. The study was terminated early due to futility.

Arm/Group Title	Dasatinib + Erlotinib
Arm/Group Description	Dasatinib orally starting dose 70 mg/day & Erlotinib 150 mg orally/day every 21 day cycle.
Period Title: Overall Study
STARTED	47
Phase I	12
Phase II	35
COMPLETED	42
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Dasatinib + Erlotinib: Phase I	Dasatinib + Erlotinib: Phase 2	Total
Arm/Group Description	Dasatinib orally starting dose 70 mg/day & Erlotinib 150 mg orally/day every 21 day cycle.	MTD from Phase I Dasatinib orally dose 70 mg/day & Erlotinib 150 mg orally/day every 21 day cycle.	Total of all reporting groups
Overall Participants	12	35	47
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61	63	62
Sex: Female, Male (Count of Participants)
Female	4 33.3%	17 48.6%	21 44.7%
Male	8 66.7%	18 51.4%	26 55.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 5.7%	2 4.3%
Not Hispanic or Latino	12 100%	33 94.3%	45 95.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 5.7%	2 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	4 11.4%	4 8.5%
White	12 100%	29 82.9%	41 87.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	35 100%	47 100%

Outcome Measures

1. Primary Outcome

Title	Phase I: Maximum Tolerable Dose (MTD) of Dasatinib Given With Erlotinib Hydrochloride
Description	MTD defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Dose-limiting toxicity (DLT) defined using NCI Common Terminology Common Terminology Criteria for Adverse Events (CTCAE) version 3 as: grade 3 or higher non-hematologic toxicity (excluding initial nausea and vomiting), grade 4 neutropenia, febrile neutropenia, or grade 4 thrombocytopenia. Grade 3-4 nausea and vomiting that cannot be controlled within 2 weeks with anti-emetics considered a DLT.
Time Frame	Baseline and at Day 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib + Erlotinib
Arm/Group Description	Dasatinib orally starting dose 70 mg/day & Erlotinib 150 mg orally/day every 21 day cycle.
Measure Participants	12
Number [mg/day]	70

2. Secondary Outcome

Title	Phase II: Number of Participant With Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Patients who have a partial or complete response or stable disease are defined as progression free. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): At least 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

One participant only received one day of therapy therefore was not evaluable for efficacy analyses; a second participant discontinued study treatment.

Arm/Group Title	Dasatinib + Erlotinib
Arm/Group Description	Dasatinib orally 70 mg/day & Erlotinib 150 mg orally/day every 21 day cycle.
Measure Participants	33
Complete Response (CR)	0 0%
Partial Response (PR)	5 41.7%
Progressive Disease (PD)	13 108.3%
Stable Disease (SD)	15 125%

3. Secondary Outcome

Title	Phase II: Progression-Free Survival (PFS) Rate
Description	A modified Thall, Simon, and Estey (1995) design used in the phase II study to monitor the proportion of patients with NSCLC who are alive and progression free (PFS) at twelve weeks after commencing treatment with dasatinib and erlotinib.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Of the 35 participants in the Phase II portion of the study, one participant received one day of therapy therefore was not evaluable for efficacy analyses; a second participant discontinued study treatment.

Arm/Group Title	Dasatinib + Erlotinib
Arm/Group Description	Dasatinib orally 70 mg/day & Erlotinib 150 mg orally/day every 21 day cycle.
Measure Participants	33
Number [Percentage of Participants]	53 441.7%

Adverse Events

Time Frame	Adverse event collection was through each 3 week treatment cycle, up to 12 weeks of assessment with treatment.
Arm/Group Title	Dasatinib + Erlotinib
Arm/Group Description	Dasatinib orally starting dose 70 mg/day & Erlotinib 150 mg orally/day every 21 day cycle.
All Cause Mortality
	Dasatinib + Erlotinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dasatinib + Erlotinib
	Affected / at Risk (%)	# Events
Total	3/47 (6.4%)
General disorders
Death	1/47 (2.1%)	1
Multi-Organ Failure	1/47 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/47 (2.1%)	1
Other (Not Including Serious) Adverse Events
	Dasatinib + Erlotinib
	Affected / at Risk (%)	# Events
Total	47/47 (100%)
Blood and lymphatic system disorders
Activated partial thromboplastin time prolonged	3/47 (6.4%)	3
Blood/Bone Marrow	1/47 (2.1%)	3
Coagulation	3/47 (6.4%)	3
Hemoglobin decreased	34/47 (72.3%)	80
Hemorrhage/Bleeding	1/47 (2.1%)	1
INR increased	1/47 (2.1%)	1
Leukopenia	4/47 (8.5%)	9
Lymphatics	1/47 (2.1%)	1
Lymphopenia	9/47 (19.1%)	34
Neutrophil count decreased	1/47 (2.1%)	1
Cardiac disorders
Arrhythmia supraventricular	1/47 (2.1%)	1
Cardiac General	2/47 (4.3%)	4
Cardiac pain	1/47 (2.1%)	1
Cardiac troponin I increased	1/47 (2.1%)	1
Chest pain	5/47 (10.6%)	6
Chest wall pain	1/47 (2.1%)	1
Electrocardiogram QTc interval prolonged	1/47 (2.1%)	1
Hypertension	9/47 (19.1%)	9
Hypotension	2/47 (4.3%)	2
Myocardial ischemia	1/47 (2.1%)	1
Nodal arrhythmia	1/47 (2.1%)	1
Ear and labyrinth disorders
Auditory/Ear	2/47 (4.3%)	2
Hearing loss	3/47 (6.4%)	3
Endocrine disorders
Endocrine	1/47 (2.1%)	1
Flushing	1/47 (2.1%)	1
Hypoparathyroidism	1/47 (2.1%)	1
Hypothyroidism	2/47 (4.3%)	2
Eye disorders
Conjunctival disorder	1/47 (2.1%)	1
Dry eye syndrome	3/47 (6.4%)	3
Gastrointestinal disorders
Abdominal pain	5/47 (10.6%)	7
Anorexia	18/47 (38.3%)	20
Colitis	1/47 (2.1%)	1
Colitis, infectious	1/47 (2.1%)	1
Constipation	17/47 (36.2%)	20
Dehydration	4/47 (8.5%)	4
Diarrhea	32/47 (68.1%)	40
Dry mouth	1/47 (2.1%)	1
Dyspepsia	2/47 (4.3%)	2
Gastritis	4/47 (8.5%)	4
Gastrointestinal	4/47 (8.5%)	4
Gastrointestinal pain	1/47 (2.1%)	1
Mucositis oral	5/47 (10.6%)	6
Nausea	30/47 (63.8%)	34
General disorders
Constitutional Symptoms	2/47 (4.3%)	2
Edema limbs	9/47 (19.1%)	10
Fatigue	38/47 (80.9%)	55
Headache	12/47 (25.5%)	13
Insomnia	8/47 (17%)	8
Oral pain	1/47 (2.1%)	1
Pain	14/47 (29.8%)	27
Pain (Other)	10/47 (21.3%)	11
Hepatobiliary disorders
Gallbladder obstruction	1/47 (2.1%)	1
Immune system disorders
Allergic rhinitis	4/47 (8.5%)	4
Infections and infestations
Infection	3/47 (6.4%)	3
Infection (Other)	3/47 (6.4%)	3
Investigations
Fever	6/47 (12.8%)	7
Metabolism and nutrition disorders
Acidosis	1/47 (2.1%)	2
Alanine aminotransferase increased	9/47 (19.1%)	10
Alkaline phosphatase increased	11/47 (23.4%)	17
Aspartate aminotransferase increased	15/47 (31.9%)	23
Bilirubin increased	4/47 (8.5%)	8
Blood glucose increased	24/47 (51.1%)	54
Blood uric acid increased	4/47 (8.5%)	4
Creatine phosphokinase increased	1/47 (2.1%)	1
Creatinine increased	13/47 (27.7%)	26
Hypercalcaemia	3/47 (6.4%)	3
Metabolic/Laboratory	11/47 (23.4%)	25
Musculoskeletal and connective tissue disorders
Back pain	4/47 (8.5%)	4
Bone pain	1/47 (2.1%)	1
Gait abnormal	1/47 (2.1%)	1
Joint pain	2/47 (4.3%)	2
Muscle weakness	1/47 (2.1%)	1
Musculoskeletal	2/47 (4.3%)	2
Neck pain	1/47 (2.1%)	1
Osteonecrosis	1/47 (2.1%)	1
Nervous system disorders
Anxiety	7/47 (14.9%)	7
Dizziness	5/47 (10.6%)	5
Neurology	1/47 (2.1%)	1
Psychiatric disorders
Depression	11/47 (23.4%)	11
Mini mental status examination abnormal	1/47 (2.1%)	1
Renal and urinary disorders
Bladder hemorrhage	1/47 (2.1%)	1
Hemorrhage urinary tract	1/47 (2.1%)	1
Reproductive system and breast disorders
Erectile dysfunction	1/47 (2.1%)	1
Hot flashes	1/47 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	1/47 (2.1%)	1
Bronchitis	1/47 (2.1%)	1
Cough	30/47 (63.8%)	34
Dysphagia	3/47 (6.4%)	3
Dyspnea	34/47 (72.3%)	64
Hemorrhage nasal	1/47 (2.1%)	1
Hypoxia	4/47 (8.5%)	5
Laryngeal hemorrhage	1/47 (2.1%)	1
Skin and subcutaneous tissue disorders
Alopecia	2/47 (4.3%)	2
Dermatology/Skin	2/47 (4.3%)	2
Dry skin	3/47 (6.4%)	3
Localized edema	1/47 (2.1%)	1
Nail disorder	1/47 (2.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.