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: June 14, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Squamous Cell 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: Phase II Trial of Dasatinib in Advanced (Stage IIIB/IV) Squamous Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Types and Frequency of DDR2 Mutations [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Determine frequency of DDR2 mutations in study patients

  • Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Establish the 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.


Enrollment: 5
Study Start Date: September 2011
Study Completion Date: May 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib
Dasatinib 140 mg by mouth each day
Drug: Dasatinib
140 mg orally, daily in 28 day cycles
Other Name: BMS-354825

Detailed Description:

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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01491633

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Bruce Johnson, MD Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Bruce Johnson, MD, Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01491633     History of Changes
Other Study ID Numbers: 11-142
Study First Received: October 5, 2011
Results First Received: May 14, 2014
Last Updated: June 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
Lung cancer
NSCLC
Stage IIIB
Stage IV

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014