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Dasatinib and Erlotinib in Non-Small Cell Lung Cancer (NSCLC)
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, March 2009
First Received: January 20, 2009   Last Updated: March 23, 2009   History of Changes
Sponsors and Collaborators: M.D. Anderson Cancer Center
Bristol-Myers Squibb
OSI Pharmaceuticals
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00826449
  Purpose

Primary Objectives:

  • For the phase I portion of the study: To assess the safety and tolerability of the combination of dasatinib and erlotinib in patients with solid tumors in order to determine the appropriate dose to carry forward for the phase II segment of the study.
  • For the phase II portion of the study: To determine the anti-tumor activity of the combination of dasatinib and erlotinib in patients with non-small cell lung cancer (NSCLC) based on the rate of progression-free survival (PFS) at twelve weeks.

Secondary Objectives:

  • To explore the relationship between clinical response to the combination of dasatinib and erlotinib and epidermal growth factor receptor (EGFR) mutational status, EGFR gene copy number, RAS mutations and expression of pSrc, pEGFR, ErbB2, ErbB3, E-cadherin, and vimentin in pre-treatment tumor biopsies.
  • To determine if there is a correlation between drug exposure, clinical response and changes in plasma levels of IL-8, bFGF, PDGF, soluble VEGFR-2, VEGF, or TNF-alpha during treatment with erlotinib and dasatinib.

Condition Intervention Phase
Lung Cancer
Non-Small Cell Lung Cancer
Drug: Dasatinib
Drug: Erlotinib
Phase I
Phase II

MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Erlotinib hydrochloride Erlotinib Dasatinib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase I-II Study of Dasatinib and Erlotinib in Non-Small Cell Lung Cancer

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Phase I: To find the highest tolerable dose of the combination of dasatinib and erlotinib hydrochloride that can be given to patients with advanced solid tumors. [ Time Frame: 6 Years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Phase II: To learn if this combination is effective when given to patients with non-small cell lung cancer. [ Time Frame: 6 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 59
Study Start Date: February 2009
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Phase I: Experimental
Dasatinib + Erlotinib
Drug: Dasatinib
Starting dose of 70 mg by mouth daily for 21 day cycle.
Drug: Erlotinib
150 mg by mouth daily every 21 day cycle.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. 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 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 [defined as amenorrhea >/=12 consecutive mths;or women on hormone replacement therapy (HRT) w/ documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL].
  10. -Continued from Inclusion #9 - 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. (Phase I only) - Histological or unequivocal cytological proof of solid tumor malignancy.
  16. (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).
  17. (Phase I only) - Prior radiotherapy is permitted (see exclusion criterion 4 for details on unallowable radiotherapy).
  18. (Phase II only) - Histological or unequivocal cytological proof of NSCLC.
  19. (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.
  20. (Phase II only) - No prior systemic therapy for recurrent or metastatic NSCLC. Prior adjuvant chemotherapy or adjuvant biologic therapy for NSCLC is acceptable if completed greater than 3 months prior to recurrence, provided that the patient has never received any EGFR or SFK inhibitors.
  21. (Phase II only) - Measurable disease as defined by RECIST criteria.
  22. (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.
  23. (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 4 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. Patients with a history of an invasive malignancy (other than the one treated in this study) that required radiotherapy or systemic treatment within the past 5 years.
  3. Patients who have received prior therapy with dasatinib, erlotinib, or another EGFR or SFK inhibitor.
  4. 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.)
  5. 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 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.
  6. Continued from Exclusion #6: (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.
  7. Patients with pericardial effusion > grade 1 (by CTCAE v3.0).
  8. 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.
  9. The patient's O^2 saturation must be >92% on room air.
  10. 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.
  11. Patients with > grade 2 neuropathy
  12. Patients with a history of pulmonary fibrosis (other than in a radiated field).
  13. Patients with inflammatory bowel disease or uncontrolled chronic diarrhea.
  14. 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.
  15. 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.

  16. 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

  17. Continued from Exclusion#16: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.
  18. Continued from Exclusion #17: (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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00826449

Contacts
Contact: Faye M. Johnson, MD, PhD, BS 713-792-6363

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Faye M. Johnson, MD, PhD, BS            
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
  More Information

Additional Information:
No publications provided

Responsible Party: UT MD Anderson Cancer Center ( Faye M. Johnson, MD, PhD, BS/Assistant Professor )
Study ID Numbers: 2008-0353
Study First Received: January 20, 2009
Last Updated: March 23, 2009
ClinicalTrials.gov Identifier: NCT00826449     History of Changes
Health Authority: United States: Food and Drug Administration

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

Study placed in the following topic categories:
Erlotinib
Thoracic Neoplasms
Respiratory Tract Diseases
Lung Neoplasms
Dasatinib
Lung Diseases
Non-small Cell Lung Cancer
Protein Kinase Inhibitors
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:
Thoracic Neoplasms
Erlotinib
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Dasatinib
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 06, 2009