Dasatinib in Treating Patients With Unresectable or Metastatic Squamous Cell Skin Cancer or RAI Stage 0-I Chronic Lymphocytic Leukemia

NCT ID: NCT00563290

Last Updated: 2015-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2014-10-31

Brief Summary

This phase II trial is studying how well dasatinib works in treating patients with unresectable or metastatic squamous cell skin cancer or RAI Stage 0-I chronic lymphocytic leukemia. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the objective response rate (complete response and partial response) in patients with unresectable or metastatic squamous cell carcinoma of the skin or RAI stage 0-I chronic lymphocytic leukemia receiving dasatinib.

SECONDARY OBJECTIVES:

I. Determine the progression-free survival of patients receiving this drug. II. Evaluate tumor for presence of total EphA2 and both total and active Src and FAK by immunohistochemistry (IHC) pre-treatment with dasatinib.

III. Evaluate tumor for presence of cyclooxygenase-2 by IHC pre-treatment with dasatinib.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

ARM I: Patients receive 100 mg dasatinib orally (PO) twice daily (BID) on days 1-28.

ARM II (PATIENTS ENROLLED AFTER 11/18/08): Patients receive 70 mg dasatinib PO BID on days 1-28.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Pre-therapy tumor biopsy specimens are collected to detect total and phosphorylated Src and FAK, total EphA2, and cyclooxygenase-2 by immunohistochemistry.

After completion of study treatment, patients are followed up monthly for up to 12 weeks.

Conditions

Recurrent Skin Cancer; Squamous Cell Carcinoma of the Skin; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (dasatinib 100 mg PO BID)

Patients receive 100 mg dasatinib PO BID on days 1-28

Group Type: EXPERIMENTAL

dasatinib

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Arm II (dasatinib 70 mg PO BID)

Patients receive 70 mg dasatinib PO BID on days 1-28

Group Type: EXPERIMENTAL

dasatinib

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

dasatinib

Given PO

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

BMS-354825; Sprycel

Eligibility Criteria

Inclusion Criteria

• Diagnosis of 1 of the following

• Histologically or cytologically confirmed squamous cell carcinoma of the skin

• Unresectable or metastatic disease
• Squamous cell histology represents ≥ 50% of the biopsy specimen
• May or may not be related to autologous or allogeneic organ transplantation
• Chronic lymphocytic leukemia (CLL)

• RAI stage 0-I
• Stable disease
• Patients with basalosquamous cell disease (basal cell with squamous differentiation) are eligible
• Measurable disease, defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
• Must be willing to undergo a pre-treatment tumor biopsy
• Brain metastases are allowed provided the following are true:

• Received definitive therapy consisting of external beam radiation therapy, gamma knife therapy, or surgical resection resulting in clinically stable disease
• Lesions are under control for at least 4 weeks after completion of definitive therapy, as measured by repeat MRI or CT scans
• No requirement for dexamethasone
• ECOG performance status 0-1 OR Karnofsky 60-100%
• Life expectancy > 6 months
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelets ≥ 100,000/mm^3
• Total bilirubin ≤ 1.5 times upper limit of normal(ULN)
• AST/ALT ≤ 2.5 times ULN
• Potassium 3.5 - 5.1 mmol/L
• Calcium > lower limit of normal
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• No known HIV 1 or HIV 2 positivity
• No known hepatitis C or hepatitis B positivity
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to dasatinib
• No QTc prolongation, defined as a QTc interval of ≥ 480 msecs or other significant ECG abnormality
• No condition that impairs the ability to swallow and retain dasatinib tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication, requirement for IV alimentation, prior surgical procedure affecting absorption, or active peptic ulcer disease)
• No clinically significant cardiovascular disease including the following:

• Myocardial infarction within 6 months
• Uncontrolled angina within 3 months
• Diagnosed or suspected congenital long QT syndrome
• Any history of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe)
• Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)
• Heart rate consistently < 50 beats/minute on pre-entry ECG
• Uncontrolled hypertension
• Ejection fraction < 45% by transthoracic echo
• No uncontrolled intercurrent illness including, but not limited to, the following:

• Ongoing or active infection requiring intravenous antibiotics
• History of significant bleeding disorder, including congenital (von Willebrand's disease) or acquired (anti-factor VIII antibodies) disorders
• Psychiatric illness or social situations that would limit compliance with study requirements
• No prior malignancy except for adequately treated basal cell cancer, carcinoma in situ of the cervix, or other cancer for which the patient has been disease free for 3 years
• No gastro-esophageal reflux disease dependent on proton pump inhibitors, H2 blockers, or antacids
• Recovered from prior therapy
• No more than 1 prior therapy with a monoclonal antibody
• No more than 1 prior chemotherapy regimen
• No prior tyrosine kinase inhibitor therapy

• Prior erlotinib hydrochloride allowed
• More than 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• At least 4 weeks since prior radiotherapy

• Measurable disease must be outside the radiotherapy port
• At least 2 weeks since prior topical therapy
• At least 4 weeks since prior surgery requiring general anesthesia and intubation
• At least 120 days (4 months) since prior amiodarone
• At least 7 days since prior and no concurrent anti-thrombotic and/or platelet agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin [full dose and 81 mg dose] and/or ibuprofen)
• At least 7 days since prior and no concurrent agents with pro-arrhythmic potential
• More than 7 days or 5 half lives, whichever is greater, since prior and no concurrent agents or substances that induce or inhibit CYP3A4
• No concurrent bisphosphonate therapy for the first 8 weeks of dasatinib treatment
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Olencki

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

NCI-2009-00226

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000576527

Identifier Type: -

Identifier Source: secondary_id

OSU-07070

Identifier Type: -

Identifier Source: secondary_id

OSU 07070

Identifier Type: OTHER

Identifier Source: secondary_id

7813

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016058

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00070

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00226

Identifier Type: -

Identifier Source: org_study_id