Sarcoma
Conditions
Keywords
AIDS-related Kaposi sarcoma, recurrent Kaposi sarcoma
Brief summary
RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with HIV-related Kaposi's sarcoma.
Detailed description
OBJECTIVES: Primary * Determine clinical response in patients with HIV-related Kaposi's sarcoma treated with imatinib mesylate. Secondary * Determine the inhibition of platelet-derived growth factor receptors, as determined by immunohistochemistry, in patients treated with this drug. * Determine cytokine profiles before and after treatment with this drug in these patients. * Determine the pharmacokinetic profile of this drug and antiretrovirals in these patients. * Determine mechanisms of primary and secondary resistance to this drug in these patients. OUTLINE: This is an open-label, multicenter study. Patients receive oral imatinib mesylate once daily. Treatment continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients are followed at 30 days. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 1 year.
Interventions
DRUGimatinib mesylate
400 mg orally once a day for up to 6 months.
Sponsors
National Cancer Institute (NCI)
The Emmes Company, LLC
AIDS Malignancy Consortium
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed Kaposi's sarcoma (KS) involving at least 1 of the following areas: * Skin * Lymph nodes * Oral cavity * Gastrointestinal tract\* * Lungs\* NOTE: \*Must be asymptomatic or minimally symptomatic AND does not require systemic cytotoxic therapy * Serological documentation of HIV infection, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), Western Blot test, or other federally approved licensed HIV test * At least 5 measurable, non-irradiated, cutaneous indicator lesions * Patients must have 3 lesions at least 5 x 5 mm that are accessible for 4 mm punch biopsy PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 60-100% Life expectancy * At least 3 months Hematopoietic * Hemoglobin ≥ 8.0 g/dL * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 75,000/mm\^3 Hepatic * AST and ALT ≤ 2.5 times upper limit of normal * Bilirubin normal * Patients with elevated bilirubin secondary to indinavir or atazanavir allowed provided total bilirubin is \< 3.5 mg/dL AND direct bilirubin is normal * No acute or known chronic liver disease (e.g., chronic active hepatitis or cirrhosis) * Hepatitis C infection with minimal or no fibrosis on liver biopsy allowed Renal * Creatinine ≤ 1.5 mg/dL OR * Creatinine clearance \> 60 mL/min Cardiovascular * No New York Heart Association class III or IV cardiac disease * No congestive heart failure * No myocardial infarction within the past 6 months Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for 3 months after study participation * No concurrent active opportunistic infection * No other severe and/or life-threatening medical disease * No other malignancy within the past 5 years except clinically insignificant malignancy not requiring active intervention, basal cell skin cancer, or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * More than 4 weeks since prior biologic therapy for KS * More than 2 weeks since prior granulocyte colony-stimulating factor * No concurrent biologic agents for KS Chemotherapy * More than 4 weeks since prior chemotherapy for KS (6 weeks for nitrosoureas or mitomycin) * No concurrent chemotherapy for KS, including systemic cytotoxic chemotherapy Endocrine therapy * No concurrent systemic corticosteroid therapy except replacement doses Radiotherapy * See Disease Characteristics * More than 4 weeks since prior radiotherapy for KS * No concurrent radiotherapy for KS Surgery * More than 2 weeks since prior major surgery Other * No prior imatinib mesylate * More than 60 days since prior local therapy to any KS indicator lesion unless the lesion has progressed since treatment * More than 4 weeks since prior investigational therapy for KS * More than 4 weeks since other prior therapy for KS * More than 14 days since prior acute treatment for an infection or other serious medical illness * No concurrent warfarin * No concurrent grapefruit juice * No other concurrent therapy for KS * No other concurrent investigational drugs * Concurrent antiretroviral therapy required except for patients who have exhausted all available treatment options
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Achieve a Clinical Response | 20-24 weeks | Clinical response = Complete Response (absence of residual disease) or Partial Response defined as no new lesions (skin or oral), or no new visceral sites of involvement (or the appearance or worsening of tumor-associated edema or effusions); AND 50% or greater decrease in the number of lesions lasting for \>4 weeks; OR Complete flattening of at least 50% of all previously raised lesions OR A 50% decrease in the sum of the products of the largest perpendicular diameters of the marker lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inhibition of Platelet-derived Growth Factor-receptor as Assessed by Immunohistochemistry | 12 months | — |
| Cytokine Profiles Before and After Imatinib Therapy | 12 months | — |
| Pharmacokinetic Profile of Imatinib and Antiretrovirals | 12 months | — |
| Mechanisms of Primary and Secondary Resistance to Imatinib Therapy | 12 months | Mutations in the juxtamembrane or kinase membrane of the c-kit or PDGF receptors at baseline or time of progression |
| Viral Transcription Profile of Kaposi's Sarcoma-associated Herpesvirus | 12 months | — |
Countries
United States
Participant flow
Recruitment details
Date of Recruitment: August 4, 2005 to August 29, 2007 at 12 AMC clinical centers
Pre-assignment details
Three patients withdrew from the study before receiving treatment.
Participants by arm
| Arm | Count |
|---|---|
| Imatinib Mesylate (Gleevec) Imatinib mesylate (Gleevec) is administered 400 mg orally once a day | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | alternative therapy | 1 |
| Overall Study | Incarcerated | 1 |
| Overall Study | Lack of Efficacy | 7 |
| Overall Study | Non-compliance | 4 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Imatinib Mesylate (Gleevec) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 43.2 years STANDARD_DEVIATION 9.5 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 30 |
| serious Total, serious adverse events | 2 / 30 |
Outcome results
Primary
Proportion of Patients Who Achieve a Clinical Response
Clinical response = Complete Response (absence of residual disease) or Partial Response defined as no new lesions (skin or oral), or no new visceral sites of involvement (or the appearance or worsening of tumor-associated edema or effusions); AND 50% or greater decrease in the number of lesions lasting for \>4 weeks; OR Complete flattening of at least 50% of all previously raised lesions OR A 50% decrease in the sum of the products of the largest perpendicular diameters of the marker lesions
Time frame: 20-24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate (Gleevec) | Proportion of Patients Who Achieve a Clinical Response | 0.33 proportion |
Secondary
Cytokine Profiles Before and After Imatinib Therapy
Time frame: 12 months
Secondary
Inhibition of Platelet-derived Growth Factor-receptor as Assessed by Immunohistochemistry
Time frame: 12 months
Secondary
Mechanisms of Primary and Secondary Resistance to Imatinib Therapy
Mutations in the juxtamembrane or kinase membrane of the c-kit or PDGF receptors at baseline or time of progression
Time frame: 12 months
Secondary
Pharmacokinetic Profile of Imatinib and Antiretrovirals
Time frame: 12 months
Secondary
Viral Transcription Profile of Kaposi's Sarcoma-associated Herpesvirus
Time frame: 12 months