Dasatinib in Treating Patients With Advanced Lung Cancer That Is No Longer Responding to Erlotinib or Gefitinib

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Drug: dasatinib

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00570401

MSKCC-06143

BMS-MSKCC-06143

P30CA008748 (U.S. NIH Grant/Contract)

Mskcc 06-143

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

Dasatinib

Experimental group

Description:

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.

Treatment:

Drug: dasatinib