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

Phase 2

Completed

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

Interventions: Drug: dasatinib
Other: laboratory biomarker analysis

Registration Number: NCT00563290

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (dasatinib 100 mg PO BID)	laboratory biomarker analysis	Patients receive 100 mg dasatinib PO BID on days 1-28
Arm II (dasatinib 70 mg PO BID)	laboratory biomarker analysis	Patients receive 70 mg dasatinib PO BID on days 1-28
Arm I (dasatinib 100 mg PO BID)	dasatinib	Patients receive 100 mg dasatinib PO BID on days 1-28
Arm II (dasatinib 70 mg PO BID)	dasatinib	Patients receive 70 mg dasatinib PO BID on days 1-28

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (Complete Response and Partial Response)	Every 2 courses during treatment, assessed up to 12 weeks after completion of treatment	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

Name	Time	Method
COX-2 Presence by IHC	At baseline	Performed per standard protocols by the Pathology Department. Samples will be obtained pre-therapy. Determination of the COX-2 tumor status on this trial will develop the beginnings of a data base upon which future therapy may be designed.
Progression-free Survival	Time from start of treatment to time of progression, assessed up to 12 weeks	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Presence of Total EphA2 and Both Total and Active Src and FAK by Immunohistochemistry (IHC)	At baseline	Performed per standard protocols by the Pathology Department.

Trial Locations

Locations (3): Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States