Clinical trial NCT00570401: Dasatinib in Treating Patients With Advanced Lung Cancer That Is No Longer Responding to Erlotinib or Gefitinib
Official title: A Phase 2 Trial of Dasatinib in Patients With Lung Adenocarcinoma With Acquired Resistance to Erlotinib or Gefitinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: adenocarcinoma of the lung
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-12-10
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with advanced lung cancer that is no longer responding to erlotinib or gefitinib.

Detailed description: OBJECTIVES:

Primary

* To determine the overall response rate (complete response and partial response) in patients with acquired erlotinib hydrochloride- or gefitinib-resistant advanced adenocarcinoma of the lung treated with dasatinib.

Secondary

* To determine the progression-free survival and overall survival of patients treated with this drug.
* To determine the overall response rate in patients with EGFR T790M lung adenocarcinomas treated with this drug.
* To determine the progression-free survival and overall survival of patients with EGFR T790M lung adenocarcinomas treated with this drug.
* To determine the toxicity profile of dasatinib in these patients.

OUTLINE: Beginning 1 week after completion of erlotinib hydrochloride or gefitinib therapy, patients receive oral dasatinib twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Response is assessed by CT scan at 4 weeks, 8 weeks, and then every 8 weeks thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Pathologically confirmed adenocarcinoma of the lung

  * Advanced disease
* Previously treated with erlotinib hydrochloride or gefitinib for 6 months (at any time) and meets 1 of the following criteria:

  * Previously received treatment with erlotinib hydrochloride or gefitinib\* and had a radiographic partial or complete response to treatment with erlotinib hydrochloride or gefitinib as defined by RECIST or WHO criteria
  * Documented mutation in EGFR from tumor DNA NOTE: \*Patients may have received other treatments subsequently including radiation or chemotherapy
* Must have developed acquired resistance to erlotinib hydrochloride or gefitinib

  * Radiographic evidence of disease progression during treatment with erlotinib hydrochloride or gefitinib
* Have previously undergone a biopsy of a site of progressive disease on protocol MSKCC 04-103\* NOTE: \*Results of this biopsy are not required to be enrolled on this trial
* Measurable indicator lesions have not been previously irradiated
* No CNS lesion that is symptomatic and/or requiring escalating doses of corticosteroids

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* WBC ≥ 3,000/mm³
* Hemoglobin ≥ 9.0 g/dL
* Platelet count ≥ 100,000/mm³
* Total bilirubin ≤ 2.0 mg/dL
* AST and ALT ≤ 2.5 times upper limit of normal
* Creatinine ≤ 2 mg/dL or creatinine clearance ≥ 55 mL/min
* QTc \< 450 msec
* Able to take oral medications
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for at least 4 weeks after study drug is stopped
* No significant medical history or unstable medical condition, including any of the following:

  * History of diagnosed congenital long QT syndrome
  * Ventricular arrhythmia
  * Congestive heart failure
  * Recent myocardial infarction
  * Unstable angina
  * Active infection
  * Uncontrolled hypertension

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 3 weeks since prior cytotoxic chemotherapy
* At least 3 weeks since prior radiation therapy to a major bone-marrow containing area
* At least 7 days since prior 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, or lidoflazine

Primary outcomes:
measure: Determine the Overall Objective Response
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Vincent A. Miller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Gregory J. Riely, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Johnson ML, Riely GJ, Rizvi NA, Azzoli CG, Kris MG, Sima CS, Ginsberg MS, Pao W, Miller VA. Phase II trial of dasatinib for patients with acquired resistance to treatment with the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib or gefitinib. J Thorac Oncol. 2011 Jun;6(6):1128-31. doi: 10.1097/JTO.0b013e3182161508.