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

Purpose

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	Intervention	Phase
Lung Cancer	Drug: dasatinib	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Erlotinib hydrochloride Erlotinib Gefitinib Dasatinib

Genetic and Rare Diseases Information Center resources: Lung Adenocarcinoma

U.S. FDA Resources

Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:

Determine the Overall Objective Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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.


Enrollment:	22
Study Start Date:	June 2006
Study Completion Date:	September 2011
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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


Ages Eligible for Study:	18 Years to 120 Years (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570401

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:

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 History of Changes
Obsolete Identifiers:	NCT00590057
Other Study ID Numbers:	Mskcc 06-143 P30CA008748 MSKCC-06143 BMS-MSKCC-06143
Study First Received:	December 7, 2007
Results First Received:	December 16, 2015
Last Updated:	December 16, 2015
Health Authority:	United States: Food and Drug Administration

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	Gefitinib Erlotinib Hydrochloride Dasatinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016