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

• ClinicalTrials.gov Identifier: NCT00570401
• Recruitment Status: Completed
• First Posted: December 10, 2007
• Results First Posted: January 22, 2016
• Last Update Posted: January 22, 2016
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer	Drug: dasatinib	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Trial of Dasatinib in Patients With Lung Adenocarcinoma With Acquired Resistance to Erlotinib or Gefitinib
• Study Start Date: June 2006
• Actual Primary Completion Date: September 2011
• Actual Study Completion Date: September 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dasatinib; 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.	Drug: dasatinib

Outcome Measures

Primary Outcome Measures :

1. Determine the Overall Objective Response [ Time Frame: 2 years ]
   To determine the overall response rate in patients with acquired erlotinib hydrochloride- or gefitinibresistant advanced adenocarcinoma of the lung treated with dasatinib using the RECIST criteria. Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.22 Changes in only the largest diameter (uni-dimensional measurement) of the tumor lesions are used in the RECIST.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Vincent A. Miller, MD; Memorial Sloan Kettering Cancer Center
• Principal Investigator: Gregory J. Riely, MD; Memorial Sloan Kettering Cancer Center

More Information

Publications of Results:

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.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00570401
• Obsolete Identifiers: NCT00590057
• Other Study ID Numbers: Mskcc 06-143; P30CA008748 ( U.S. NIH Grant/Contract ); MSKCC-06143; BMS-MSKCC-06143
• First Posted: December 10, 2007
• Results First Posted: January 22, 2016
• Last Update Posted: January 22, 2016
• Last Verified: December 2015

Keywords provided by Memorial Sloan Kettering Cancer Center:

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

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Dasatinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action