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Phase II Study of Dasatinib in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Phase 2
18 Years
Open (Enrolling)
Non Small Cell Lung Cancer

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Trial Information

Phase II Study of Dasatinib in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer death in the United States. Twenty to
seventy-five percent of patients initially treated with surgery or radiotherapy recur and
become candidates for systemic therapy. Src expression has been identified in a majority of
NSCLC cell lines and may be important in hypoxic growth and angiogenesis of NSCLC.

This phase II trial will investigate the activity of the oral Src inhibitor dasatinib in
advanced stage NSCLC. We hypothesize that the inhibition of Src pathway with dasatinib will
show anti-tumor activity in advanced NSCLC, with a tolerable safety profile.

Fresh frozen tissue is needed for the genomics analysis, thus a biopsy will be required to
participate in this trial. The genomic analysis will determine if the tumor is Src-active or
Src-inactive and responses to dasatinib compared. In stage I, 40 patients will be treated
without prior knowledge of their tumoral Src-activity. If all stage I responses are observed
in the Src-active patients, the second stage will only accrue that cohort. If all responses
are observed in the Src-inactive cohort, the activity of dasatinib and genomic determination
of dasatinib response will be re-evaluated. Otherwise, if during Stage I, responses are
observed in both cohorts, they will be accrued separately and evaluated in a two-stage

Dasatinib will be give orally twice daily and continue until progression of disease,
intolerable toxicity or patient withdrawal. Imaging studies will be done pre-treatment then
every 6 weeks to assess radiologic response to therapy.

Patients will be followed for 30 days after the last dose of dasatinib to assess toxicity.

Inclusion Criteria:

1. Histological/cytological documented non-small cell lung cancer (NSCLC). Documentation
of recurrence required if treated with surgical resection and/or external beam
radiation therapy (XRT) with curative intent and now have recurrent disease.

2. Fresh tissue biopsy material for genomics analysis prior to initiating dasatinib. If
prior XRT, tissue biopsy must be outside XRT field. Biopsy must be after any prior

3. Prior treatment (tx) to include one of the following:

- At least 1 prior systemic regimen (IV or oral agent) for Stage IV NSCLC or for
recurrent disease.

- Recurrence within 12 months after completion of systemic neoadjuvant/adjuvant
chemotherapy for early stage NSCLC.

- Combined modality platinum-based tx for Stage III NSCLC.

4. Prior XRT permitted if ≥1 week since completion, XRT must be <25% of bone marrow

5. At least one, non-radiated, measurable lesion (per RECIST).

6. Age ≥18 years.

7. Eastern Cooperative Oncology Group (ECOG) 0-2.

8. Adequate Organ Function:

1. Total bilirubin < Upper limit normal (ULN)

2. Hepatic enzymes (AST, ALT) ≤2.5x ULN

3. Serum creatinine <1.5x ULN

4. Hemoglobin ≥9 gm/dL

5. Neutrophil count (ANC/AGC) ≥1500 per μL

6. Platelets ≥100,000 per μL

7. Prothrombin time (PT)/a Partial thromboplastin time (PTT) ≤1.5x control

9. No other serious medical or psychiatric illness.

10. Ability to take oral medication (dasatinib must be swallowed whole).

11. Women of childbearing potential must have negative serum pregnancy test ≤72 hours and
not >7 days prior to starting study drug.

12. Sexually active males and females of reproductive potential must agree to use
adequate method of contraception during tx and for at least 4 weeks after study drug

13. Signed, written informed consent including Health Insurance Portability and
Accountability Act (HIPAA) according to institutional guidelines.

Exclusion Criteria:

1. Previous or concomitant malignancy in past 2 years other than curatively treated
carcinoma in situ of cervix, or basal cell/squamous cell carcinoma of the skin.

2. Prior tx with dasatinib or other agents that inhibit Src.

3. Evidence of symptomatic pleural effusions (grade 2) unless undergo therapeutic
thoracentesis as part of non-study care. Successful pleurodesis allowed. Patients who
require supplemental oxygen or with oxygen saturation on room air <89% are not
eligible. Pericardial effusions of any grade are not eligible.

4. Untreated documented symptomatic central nervous system (CNS) metastases.

5. Cardiac Symptoms:

1. Uncontrolled angina, congestive heart failure(CHF)or myocardial infarction
within 6 months

2. Diagnosed congenital long QT syndrome

3. Any h/o clinically significant ventricular arrhythmias

4. Prolonged QT corrected (QTc) interval on pre-entry EKG (>450 msec)

5. Uncontrolled B/P as defined as >160/90 on B/P therapy

6. Hypokalemia or hypomagnesaemia if it cannot be corrected.

7. H/o diagnosed congenital acquired bleeding disorders.

8. Ongoing or recent (≤3 months) significant (≥grade 3) GI bleeding.

9. Con Meds:

1. Drugs having risk of causing Torsades de Pointes (must stop drug 7 days before

2. Current therapeutic dose unfractionated heparin, low-molecular weight heparin,
or coumadin therapy;

3. St. John's Wort must be stopped while on dasatinib;

4. IV bisphosphonates stopped 2 weeks pre/6 weeks post dasatinib.

10. Prisoners/subjects compulsorily detained for tx of psychiatric and/or physical

11. Pregnant or breastfeeding.

12. Active or uncontrolled infection requiring IV antibiotics.

13. Impairment of GI function/disease that may alter absorption of dasatinib (e.g.,
ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome,
or small bowel resection).

14. Received investigational drugs ≤4 weeks prior to starting study drug and/or not
recovered from side effects of such therapy. Any other anti-neoplastic and/or
molecular therapy must be discontinued 7 days prior to starting dasatinib.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine ability of Src pathway signature to predict tumor response associated with dasatinib treatment in previously treated patients with advanced NSCLC.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Michael Kelley, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Institutional Review Board

Study ID:




Start Date:

September 2008

Completion Date:

January 2014

Related Keywords:

  • Non Small Cell Lung Cancer
  • Lung Cancer
  • Dasatinib
  • Genomics
  • Genomics analysis
  • Genomic signature
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Duke University Medical Center Durham, North Carolina  27710
Durham VA Medical Center Durham, North Carolina  27705
Duke Raleigh Raleigh, North Carolina  27609