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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00563290
First received: November 22, 2007
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

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


Condition Intervention Phase
Recurrent Skin Cancer
Squamous Cell Carcinoma of the Skin
Stage 0 Chronic Lymphocytic Leukemia
Stage I Chronic Lymphocytic Leukemia
Drug: dasatinib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Dasatinib in Patients With Transplant and Non-Transplant Related Unresectable or Metastatic Cutaneous Squamous Cell Carcinoma and RAI Stage 0-1 Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response rate (complete response and partial response) [ Time Frame: Every 2 courses during treatment, assessed up to 12 weeks after completion of treatment ] [ Designated as safety issue: No ]
    Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The evaluation of response will be measured in subjects with CLL by using CT scans, just as in Standard of Care. Should patients demonstrate response to dasatinib, we will perform inferential comparisons using usual statistical methods.


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Time from start of treatment to time of progression, assessed up to 12 weeks ] [ Designated as safety issue: No ]
    Progression will be evaluated in this study using the new international criteria proposed by the RECIST Committee. Analysis will be preliminary to provide and estimate of variability of endpoints in the patient population for which previous data are not available

  • Presence of total EphA2 and both total and active Src and FAK by immunohistochemistry (IHC) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Performed per standard protocols by the Pathology Department.

  • COX-2 presence by IHC [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 35
Study Start Date: November 2007
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (kinase inhibitor therapy)
Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: dasatinib
Other Names:
  • BMS-354825
  • Sprycel
Other: laboratory biomarker analysis
Correlative studies

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: This is a multicenter study. Patients are stratified according to squamous cell carcinoma of the skin origin (transplantation vs nontransplantation).

Patients receive oral dasatinib twice daily on days 1-28. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00563290

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas Olencki Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00563290     History of Changes
Other Study ID Numbers: NCI-2009-00226, OSU 07070, N01CM00070
Study First Received: November 22, 2007
Last Updated: March 18, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Carcinoma, Squamous Cell
Skin Neoplasms
Leukemia
Carcinoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Neoplasms by Site
Skin Diseases
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014