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Phase II Study Evaluating The Safety And Response To Neoadjuvant Dasatinib In Early Stage Non-Small Cell Lung Cancer (NSCLC).

Phase 2
18 Years
Not Enrolling
Carcinoma, Non-Small-Cell Lung

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Trial Information

Phase II Study Evaluating The Safety And Response To Neoadjuvant Dasatinib In Early Stage Non-Small Cell Lung Cancer (NSCLC).

This is a phase II study of dasatinib, a targeted biologic agent, known to inhibit Src. It
is difficult to assess outcome in phase II adjuvant trials because there is no measurable
disease to evaluate efficacy and there are many variables that could confound comparing
survival of subjects on trial to historical controls. Therefore, after a fresh frozen tumor
tissue sample is obtained for genomic analysis, we plan to treat subjects with neoadjuvant
dasatinib and then measure tumor response to therapy prior to surgery. Resected tumor will
also be assessed for pathologic response as well as for changes in genomic expression

Subjects will be treated with neoadjuvant dasatinib 70 mg PO twice daily for 3 weeks, with a
mandatory minimum of 3 days (72 hours) off of study drug prior to surgical resection.
Imaging studies will be done pre-treatment and pre-surgery to assess radiologic response to
therapy. The surgical specimen will be evaluated for pathologic response. A tumor tissue
sample will be obtained from the surgical specimen for genomic analysis and will be
evaluated for changes in genomic expression profiles.

Patients whose tumors have a response to neoadjuvant dasatinib therapy might benefit with
better cancer control if they receive a potentially therapeutic course of adjuvant
dasatinib. Patients that have at least a 15% decrease or better objective response, without
evidence of progression to neoadjuvant dasatinib (per tumor evaluation pre-surgery) or
pathologic response (as defined as ≥30% tumor necrosis or cell death) to neoadjuvant
dasatinib therapy will be eligible to receive dasatinib 70 mg twice daily for 90 days after
the completion of standard adjuvant therapy or after recovery from surgery if no standard
adjuvant therapy is given. Patients will be followed for approximately 30 days after the
last dose of dasatinib to assess toxicity.

Response will be evaluated in Src regulated and Src deregulated cohorts of tumors. If
responses to neoadjuvant dasatinib occur, then accrual to either or both cohorts will be
expanded. If there are no responses to neoadjuvant dasatinib in the cohort groups, then
accrual to either or both cohorts will be stopped. The results of this study may be useful
in designing future studies in early stage NSCLC using dasatinib alone or in combination
with chemotherapy.

Inclusion Criteria:

- Suspected or histological/cytological diagnosis of Non-Small Cell Lung Cancer
(NSCLC), Stage IB (≥4 cm per CT) or Stage IIA or IIB, amenable to surgical resection

- Must be deemed a surgical candidate

- Tumors ≥2 cm in maximum diameter without radiographic, bronchoscopic or pathologic
evidence of nodal metastases are eligible for biopsy

- Fresh tissue biopsy material must be available for genomics analysis prior to
initiating dasatinib therapy

- Age ≥18 years

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

- No prior chemotherapy, immunotherapy, radiation therapy or biologic/targeted therapy
for any malignancy

- Adequate Organ Function:

- Total bilirubin
- Hepatic enzymes (AST, ALT) ≤2.5x institutional ULN

- Serum creatinine <1.5x institutional ULN

- Hemoglobin ≥9 gm/dL

- Neutrophil count (ANC or AGC) ≥1500 per μL

- Platelets ≥100,000 per μL

- Prothrombin time (PT)/a partial thromboplastin time (PTT) ≤1.5x control

- No other serious medical or psychiatric illness

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

- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
preferably within 72 hours and no later than 7 days, prior to the start of study drug

- Both sexually active males and females of reproductive potential must agree to use an
adequate method of contraception throughout treatment and for at least 4 weeks after
study drug is stopped

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

Exclusion Criteria:

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

- Prior dasatinib therapy

- Evidence of pleural or pericardial effusion of any grade

- Cardiac Symptoms:

- Uncontrolled angina, congestive heart failure (CHF), or myocardial infarction
(MI) within 6 months

- Diagnosed congenital long QT syndrome

- Any history of clinically significant ventricular arrhythmias (such as
ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)

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

- Uncontrolled hypertension defined as >160/90 on a regimen of antihypertensive

- Subjects with hypokalemia or hypomagnesaemia if it cannot be corrected

- History of diagnosed congenital acquired bleeding disorders (e.g., von Willebrand's

- Ongoing or recent (≤3 months) significant (≥grade 3) gastrointestinal bleeding

- Concomitant Medications:

- Drugs that are generally accepted to have a risk of causing Torsades de Pointes
including: (Patients must discontinue drug 7 days prior to starting dasatinib)

**quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide,
dofetilide, erythromycin, clarithromycin, chlorpromazine, haloperidol,
mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol,
methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl,
pentamidine, sparfloxacin, lidoflazine

- Current therapeutic dose heparin or coumadin therapy

- St. John's Wort and all herbal supplements must be stopped while on dasatinib

- IV bisphosphonates will be withheld for 2 weeks prior and 6 weeks after
dasatinib administration due to risk of hypocalcaemia

- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness

- Pregnant or breastfeeding

- Active or uncontrolled infection requiring intravenous antibiotics

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

- Patients who have received investigational drugs ≤4 weeks prior to starting study
drug and/or who have not recovered from side effects of such therapy

Type of Study:


Study Design:

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

Outcome Measure:

Response Rate

Outcome Description:

Response rate (radiologic and pathologic) in Stage IB and II to neoadjuvant dasatinib

Outcome Time Frame:

First progression and survival every 3 months for 2 years, then every 6 months until 5 years, then yearly.

Safety Issue:


Principal Investigator

Neal Ready, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Institutional Review Board

Study ID:




Start Date:

November 2007

Completion Date:

September 2009

Related Keywords:

  • Carcinoma, Non-Small-Cell Lung
  • Non Small Cell Lung Cancer (NSCLC)
  • carcinoma
  • dasatinib
  • neoadjuvant
  • adjuvant
  • resection
  • genomic signature
  • predictor
  • microarray
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Duke University Medical CenterDurham, North Carolina  27710