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.

Study Overview

• Status: Terminated
• Conditions: Squamous Cell Lung Cancer
• Intervention / Treatment: Drug: Dasatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dasatinib; Dasatinib 140 mg by mouth each day	Drug: Dasatinib; 140 mg orally, daily in 28 day cycles; Other Names: BMS-354825

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Determine the overall response rate of patients with squamous cell carcinoma of the lung treated with dasatinib	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Types and Frequency of DDR2 Mutations	Determine frequency of DDR2 mutations in study patients	2 years
Survival	Establish the overall survival of patients with SCC treated with dasatinib	2 years
Toxicities	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.	2 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Bruce Johnson, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Brunner AM, Costa DB, Heist RS, Garcia E, Lindeman NI, Sholl LM, Oxnard GR, Johnson BE, Hammerman PS. Treatment-related toxicities in a phase II trial of dasatinib in patients with squamous cell carcinoma of the lung. J Thorac Oncol. 2013 Nov;8(11):1434-7. doi: 10.1097/JTO.0b013e3182a47162.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: October 5, 2011
• First Submitted That Met QC Criteria: December 12, 2011
• First Posted (Estimate): December 14, 2011

Study Record Updates

• Last Update Posted (Estimate): July 15, 2014
• Last Update Submitted That Met QC Criteria: June 14, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: NSCLC; Lung cancer; Stage IV; Stage IIIB
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: 11-142