Clinical trial NCT00563290: Dasatinib in Treating Patients With Unresectable or Metastatic Squamous Cell Skin Cancer or RAI Stage 0-I Chronic Lymphocytic Leukemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Skin Cancer
Squamous Cell Carcinoma of the Skin
Stage 0 Chronic Lymphocytic Leukemia
Stage I Chronic Lymphocytic Leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-11-26
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate (Complete Response and Partial Response)
timeFrame: Every 2 courses during treatment, assessed up to 12 weeks after completion of treatment
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Time from start of treatment to time of progression, assessed up to 12 weeks
measure: Presence of Total EphA2 and Both Total and Active Src and FAK by Immunohistochemistry (IHC)
timeFrame: At baseline
measure: COX-2 Presence by IHC
timeFrame: At baseline
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: Ohio State University
name: Thomas Olencki
role: PRINCIPAL_INVESTIGATOR
References: