Dasatinib in Advanced Squamous Cell Lung Cancer

This study has been terminated.
(Safety issues/concerns per DF/HCC PI)
Sponsor:
Information provided by (Responsible Party):
Bruce Johnson, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01491633
First received: October 5, 2011
Last updated: February 13, 2014
Last verified: February 2014

October 5, 2011
February 13, 2014
September 2011
January 2013   (final data collection date for primary outcome measure)
Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Determine the overall response rate of patients with squamous cell carcinoma of the lung treated with dasatinib
Same as current
Complete list of historical versions of study NCT01491633 on ClinicalTrials.gov Archive Site
  • Types and frequency of DDR2 mutations [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Characterize the types and frequency of DDR2 mutations in study patients and correlate mutation status of DDR2 with clinical characteristics and response to therapy
  • Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Establish the progression-free and overall survival of patients with SCC treated with dasatinib
  • Toxicities [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Define the toxicities of dasatinib when administered to the patient population. NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 will be utilized for adverse event reporting.
Same as current
Not Provided
Not Provided
 
Dasatinib in Advanced Squamous Cell Lung Cancer
Phase II Trial of Dasatinib in Advanced (Stage IIIB/IV) Squamous Cell Lung Cancer

Dasatinib is a drug that has been shown to stop some cancer cells from growing. This drug has been used in treatment for other types of cancer and information from other research studies suggests that dasatinib may help to stop squamous cell lung cancer from growing, especially in individuals whose tumor has a mutation in the DDR2 gene.

Advanced squamous cell lung cancer (SqCC) carries a poor prognosis and new therapeutic targets are needed. Several studies have examined dasatinib in NSCLC; these report significant toxicities, but also responses in patients found to harbor mutations in DDR2 or BRAF.

An open-label phase II trial with dasatinib was carried out to determine the response rates in patients with SqCC who had previously failed standard chemotherapy and to correlate responses with patient genotype.

Dasatinib will be taken orally, daily in cycles of 28 days.

On the first day of study treatment and at 2 weeks, 4 weeks and then every 4 weeks subjects will have the following:

  • Medical history and clinical exam
  • Safety blood tests
  • Measurement of Performance Status
  • Review of pill log
  • CT scans will be done every 8 weeks.

The study was halted after enrolling 5 patients, all of whom were discontinued from the trial due to excess toxicity of dasatinib administered at 140mg per day. The patients were treated for 9, 14, 24, 40, and 42 days. 3 of 5 (60%) patients experienced ≥ grade 3 toxicities (dyspnea, fatigue, AST elevation, anorexia, nausea). Intolerable grade 2 pleural effusions were noted in 2 of 5 patients. 4 of 5 patients died after 44, 52, 127, and 226 days; one patient remains alive at 279 days. No deaths were associated with the study drug.

In this research study, the investigators are looking at how well dasatinib works in treating squamous cell lung cancer.

Dasatinib administered at 140mg per day for the treatment of advanced SqCC of the lung is associated with excess adverse events, similar to other studies, so is not recommended in unselected patients. Further work to identify patients likely to benefit from dasatinib and in managing dasatinib-related toxicities is needed.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Squamous Cell Lung Cancer
Drug: Dasatinib
140 mg orally, daily in 28 day cycles
Other Name: BMS-354825
Experimental: Dasatinib
Dasatinib 140 mg by mouth each day
Intervention: Drug: Dasatinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
5
May 2013
January 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Stage III/B or IV squamous NSCLC
  • Measurable disease
  • Previously offered all standard chemotherapy regimens for advanced squamous cell lung cancer
  • ECOG performance status of 0 or 1
  • Estimated life expectancy greater than 12 weeks
  • Normal organ and marrow function
  • Confirmed availability of archival pathology samples
  • Agrees to discontinue St. Johns Wort
  • Able to take medications by mouth
  • Willing and able to use acceptable method of birth control for the entire study period and for at least 4 weeks after the last dose of study drug

Exclusion Criteria:

  • Pregnant or breast-feeding
  • Chemotherapy or radiotherapy within 4 weeks prior to entering study
  • Receiving any other investigational agents
  • Known untreated or progressive brain metastases
  • History of prior treatment with or allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib, nilotinib or imatinib
  • Taking medications known to be potent CYP3A4 inhibitors
  • Currently taking H2 inhibitors or proton pump inhibitors
  • Currently taking drugs or have taken drugs in the past 7 days that are generally accepted to have a risk of causing Torsades de Pointes
  • HIV positive
  • Clinically uncontrolled hypertension (blood pressure > 160/110)
  • Previous or concurrent malignancy except adequately treated basal or squamous cell skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 5 years
  • Active and uncontrolled clinically significant infection
  • Chronic gastrointestinal disease
  • Acquired or congenital bleeding disorder or clinically significant gastrointestinal bleeding within 3 months
  • Supplemental oxygen required for current malignancy
  • Evidence of symptomatic pleural effusions unless undergoing a therapeutic thoracentesis as part of non-study care
  • Individuals who are prisoners or who are compulsory detained for medical or psychiatric reasons
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Hypokalemia or hypomagnesemia that cannot be corrected prior to dasatinib administration
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01491633
11-142
Yes
Bruce Johnson, MD, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
Not Provided
Principal Investigator: Bruce Johnson, MD Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP