Dasatinib in Advanced Squamous Cell Lung Cancer

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01491633
• Collaborator: (none)
• Enrollment: 5
• Locations: 3
• Arm: 1
• Duration (Months): 20
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Squamous Cell Lung Cancer	Drug: Dasatinib	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Dasatinib in Advanced (Stage IIIB/IV) Squamous Cell Lung Cancer
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Response Rate [2 years]

   Determine the overall response rate of patients with squamous cell carcinoma of the lung treated with dasatinib

Secondary Outcome Measures

1. Types and Frequency of DDR2 Mutations [2 years]

   Determine frequency of DDR2 mutations in study patients

2. Survival [2 years]

   Establish the overall survival of patients with SCC treated with dasatinib

3. Toxicities [2 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Dana-Farber Cancer Institute

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bruce Johnson, MD, Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01491633
• Other Study ID Numbers: 11-142
• First Posted: Dec 14, 2011
• Last Update Posted: Jul 15, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by Bruce Johnson, MD, Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute: Lung cancer; NSCLC; Stage IIIB; Stage IV
• Additional relevant MeSH terms: Lung Neoplasms; Dasatinib

Study Results

Participant Flow

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 140 mg by mouth each day Dasatinib: 140 mg orally, daily in 28 day cycles
Period Title: Overall Study
STARTED	5
COMPLETED	0
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 140 mg by mouth each day Dasatinib: 140 mg orally, daily in 28 day cycles
Overall Participants	5
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 140 mg by mouth each day Dasatinib: 140 mg orally, daily in 28 day cycles
Measure Participants	5
Number [percent]	NA

2. Secondary Outcome

Title	Types and Frequency of DDR2 Mutations
Description	Determine frequency of DDR2 mutations in study patients
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 140 mg by mouth each day Dasatinib: 140 mg orally, daily in 28 day cycles
Measure Participants	5
Number [participants]	0 0%

3. Secondary Outcome

Title	Survival
Description	Establish the overall survival of patients with SCC treated with dasatinib
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

One subject who was alive at the end of the study was censored from the survival analysis

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 140 mg by mouth each day Dasatinib: 140 mg orally, daily in 28 day cycles
Measure Participants	4
Mean (Standard Deviation) [days]	112 (85)

4. Secondary Outcome

Title	Toxicities
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 140 mg by mouth each day Dasatinib: 140 mg orally, daily in 28 day cycles
Measure Participants	5
Number [grade 3 toxicities]	3

5. Post-Hoc Outcome

Title	Time on Study
Description	Number of days participant remained on study
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 140 mg by mouth each day Dasatinib: 140 mg orally, daily in 28 day cycles
Measure Participants	5
Mean (Standard Deviation) [days]	22 (12)

Adverse Events

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 140 mg by mouth each day Dasatinib: 140 mg orally, daily in 28 day cycles
All Cause Mortality
	Dasatinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dasatinib
	Affected / at Risk (%)	# Events
Total	2/5 (40%)
General disorders
Death	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Hemoptysis	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Dasatinib
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Gastrointestinal disorders
Elevated LFTs	1/5 (20%)	1
Nausea	1/5 (20%)	1
General disorders
Fatigue	1/5 (20%)	1
Anorexia	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/5 (40%)	2
Dyspnea	1/5 (20%)	1

Limitations/Caveats

Due to the toxicity of the study agent no subjects were evaluable for response

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.