Imatinib Mesylate in Treating Patients With HIV-Related Kaposi's Sarcoma

• Sponsor: AIDS Malignancy Consortium (Other)
• Overall Status: Completed
• CT.gov ID: NCT00090987
• Collaborator: National Cancer Institute (NCI) (NIH), The Emmes Company, LLC (Industry)
• Enrollment: 30
• Locations: 15
• Arm: 1
• Duration (Months): 54
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Drug: imatinib mesylate	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial Of Imatinib Mesylate (Gleevec) In Patients With HIV Related Kaposi's Sarcoma
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Imatinib mesylate Imatinib mesylate (Gleevec) taken 400 mg orally once a day for up to 6 months	Drug: imatinib mesylate; 400 mg orally once a day for up to 6 months.; Other Names: Gleevec

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Inhibition of Platelet-derived Growth Factor-receptor as Assessed by Immunohistochemistry [12 months]

2. Cytokine Profiles Before and After Imatinib Therapy [12 months]

3. Pharmacokinetic Profile of Imatinib and Antiretrovirals [12 months]

4. 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

5. Viral Transcription Profile of Kaposi's Sarcoma-associated Herpesvirus [12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
2	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
3	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
4	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California	United States	92262
5	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
6	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida	United States	33136
7	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
8	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
9	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
10	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
11	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
12	Memorial Sloan - Kettering Cancer Center	New York	New York	United States	10021
13	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
14	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19106
15	Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center	Seattle	Washington	United States	98101

Sponsors and Collaborators

• AIDS Malignancy Consortium
• National Cancer Institute (NCI)
• The Emmes Company, LLC

Investigators

• Study Chair: Ariela Noy, MD, Memorial Sloan Kettering Cancer Center
• Study Chair: Henry Koon, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 24, 2007

More Information

Publications

• Berman E, Nicolaides M, Maki RG, Fleisher M, Chanel S, Scheu K, Wilson BA, Heller G, Sauter NP. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med. 2006 May 11;354(19):2006-13.
• Kerkelä R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, Walters B, Shevtsov S, Pesant S, Clubb FJ, Rosenzweig A, Salomon RN, Van Etten RA, Alroy J, Durand JB, Force T. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006 Aug;12(8):908-16. Epub 2006 Jul 23.
• Koon HB, Krown SE, Lee JY, Honda K, Rapisuwon S, Wang Z, Aboulafia D, Reid EG, Rudek MA, Dezube BJ, Noy A. Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042. J Clin Oncol. 2014 Feb 10;32(5):402-8. doi: 10.1200/JCO.2012.48.6365. Epub 2013 Dec 30.

• Responsible Party: AIDS Malignancy Consortium
• ClinicalTrials.gov Identifier: NCT00090987
• Other Study ID Numbers: AMC-042; U01CA070019; CDR0000380955
• First Posted: Sep 8, 2004
• Last Update Posted: Jun 6, 2018
• Last Verified: May 1, 2018

• Keywords provided by AIDS Malignancy Consortium: AIDS-related Kaposi sarcoma; recurrent Kaposi sarcoma
• Additional relevant MeSH terms: Sarcoma, Kaposi; Sarcoma; Imatinib Mesylate

Study Results

Participant Flow

Recruitment Details	Date of Recruitment: August 4, 2005 to August 29, 2007 at 12 AMC clinical centers
Pre-assignment Detail	Three patients withdrew from the study before receiving treatment.

Arm/Group Title	Imatinib Mesylate (Gleevec)
Arm/Group Description	Imatinib mesylate (Gleevec) is administered 400 mg orally once a day
Period Title: Overall Study
STARTED	30
COMPLETED	9
NOT COMPLETED	21

Baseline Characteristics

Arm/Group Title	Imatinib Mesylate (Gleevec)
Arm/Group Description	Imatinib mesylate (Gleevec) is administered 400 mg orally once a day
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	29 96.7%
>=65 years	1 3.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.2 (9.5)
Sex: Female, Male (Count of Participants)
Female	1 3.3%
Male	29 96.7%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Who Achieve a Clinical Response
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imatinib Mesylate (Gleevec)
Arm/Group Description	Imatinib mesylate (Gleevec) is administered 400 mg orally once a day
Measure Participants	30
Number [proportion]	0.33

2. Secondary Outcome

Title	Inhibition of Platelet-derived Growth Factor-receptor as Assessed by Immunohistochemistry
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Cytokine Profiles Before and After Imatinib Therapy
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Pharmacokinetic Profile of Imatinib and Antiretrovirals
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Mechanisms of Primary and Secondary Resistance to Imatinib Therapy
Description	Mutations in the juxtamembrane or kinase membrane of the c-kit or PDGF receptors at baseline or time of progression
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Viral Transcription Profile of Kaposi's Sarcoma-associated Herpesvirus
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Imatinib Mesylate (Gleevec)
Arm/Group Description	Imatinib mesylate (Gleevec) is administered 400 mg orally once a day
All Cause Mortality
	Imatinib Mesylate (Gleevec)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Imatinib Mesylate (Gleevec)
	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)
Blood and lymphatic system disorders
Hemorrhage	1/30 (3.3%)	1
Infections and infestations
Infection	1/30 (3.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary malignancy	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Imatinib Mesylate (Gleevec)
	Affected / at Risk (%)	# Events
Total	20/30 (66.7%)
Blood and lymphatic system disorders
Blood/Bone Marrow	2/30 (6.7%)	3
Edema, limb	6/30 (20%)	8
Hemoglobin	6/30 (20%)	7
Leukocytes (total WBC)	4/30 (13.3%)	6
Neutrophil Count	4/30 (13.3%)	7
Platelets	2/30 (6.7%)	2
Gastrointestinal disorders
Anorexia	3/30 (10%)	3
Constipation	2/30 (6.7%)	2
Diarrhea	6/30 (20%)	7
Gastrointestinal, other	2/30 (6.7%)	2
Nausea	10/30 (33.3%)	14
Pain, abdominal	2/30 (6.7%)	2
Taste Alteration	2/30 (6.7%)	2
Vomiting	6/30 (20%)	9
Abdominal bloating	2/30 (6.7%)	2
General disorders
Fatigue	5/30 (16.7%)	8
Insomnia	2/30 (6.7%)	2
Metabolism and nutrition disorders
ALT, SGPT	2/30 (6.7%)	2
Alkaline Phosphatase	3/30 (10%)	3
Amylase	3/30 (10%)	10
CPK	3/30 (10%)	4
Hyperbilirubinemia	5/30 (16.7%)	10
Hyperglycemia	4/30 (13.3%)	6
Hypocalcemia	2/30 (6.7%)	4
Hypokalemia	4/30 (13.3%)	5
Hypophosphatemia	4/30 (13.3%)	9
Metabolic/laboratory other	3/30 (10%)	4
Musculoskeletal and connective tissue disorders
Pain, back	2/30 (6.7%)	2
Pain, extremity	6/30 (20%)	6
Pain, muscle	3/30 (10%)	4
Nervous system disorders
Dizziness	2/30 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Cough	3/30 (10%)	4
Dyspnea	2/30 (6.7%)	2
Pain, chest	3/30 (10%)	3
Skin and subcutaneous tissue disorders
Bruising	2/30 (6.7%)	2
Dermatology/skin, other	2/30 (6.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.