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

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00563290
Enrollment
7
Registered
2007-11-26
Start date
2007-11-30
Completion date
2014-10-31
Last updated
2015-06-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

DRUGdasatinib

Given PO

OTHERlaboratory biomarker analysis

Correlative studies

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Objective Response Rate (Complete Response and Partial Response)Every 2 courses during treatment, assessed up to 12 weeks after completion of treatmentPer 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

MeasureTime frameDescription
Progression-free SurvivalTime from start of treatment to time of progression, assessed up to 12 weeksProgression 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 baselinePerformed per standard protocols by the Pathology Department.
COX-2 Presence by IHCAt baselinePerformed 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.

Countries

United States

Participant flow

Participants by arm

ArmCount
Arm I Dasatinib
Patients receive oral dasatinib 100 mg twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
3
Arm II Dastinib
Patients receive oral dasatinib 70 mg twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
4
Total7

Baseline characteristics

CharacteristicArm I DasatinibArm II DastinibTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
2 Participants0 Participants2 Participants
Age, Categorical
Between 18 and 65 years
1 Participants4 Participants5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
3 Participants4 Participants7 Participants
Sex: Female, Male
Female
1 Participants2 Participants3 Participants
Sex: Female, Male
Male
2 Participants2 Participants4 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
1 / 31 / 4
serious
Total, serious adverse events
0 / 30 / 4

Outcome results

Primary

Objective Response Rate (Complete Response and Partial Response)

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.

Time frame: Every 2 courses during treatment, assessed up to 12 weeks after completion of treatment

ArmMeasureValue (NUMBER)
Arm I: DasatinibObjective Response Rate (Complete Response and Partial Response)0 percentage of patients
Arm II: DasatinibObjective Response Rate (Complete Response and Partial Response)0 percentage of patients
Secondary

COX-2 Presence by IHC

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.

Time frame: At baseline

Population: Funding was not available to do correlative studies

Secondary

Presence of Total EphA2 and Both Total and Active Src and FAK by Immunohistochemistry (IHC)

Performed per standard protocols by the Pathology Department.

Time frame: At baseline

Population: Funding was not available to do correlative studies

Secondary

Progression-free Survival

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

Time frame: Time from start of treatment to time of progression, assessed up to 12 weeks

Population: The second treatment arm of Dasatinib 70 mg orally twice a day was created as a result of an amendment to the protocol therefore the patient PFS data was combined for each arm.

ArmMeasureValue (MEDIAN)
Arm I: DasatinibProgression-free Survival4 weeks

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026