Pegylated Liposomal Doxorubicin Hydrochloride and Bevacizumab in Treating Patients with Advanced Kaposi Sarcoma

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IITreatment18 and over09-C-0130
NCI-2013-01450, 090130, NCT00902239, P09493, NCT00923936

Trial Description

Summary

This pilot phase II trial studies pegylated liposomal doxorubicin hydrochloride and bevacizumab in treating patients with Kaposi sarcoma that has spread to other places in the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, or stopping them from dividing, or by stopping them from spreading. Pegylated liposomal doxorubicin hydrochloride may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Bevacizumab may stop the growth of Kaposi sarcoma by blocking the growth of new blood vessels necessary for tumor growth. Giving pegylated liposomal doxorubicin hydrochloride with bevacizumab may be a better treatment for Kaposi sarcoma.

Further Study Information

PRIMARY OBJECTIVES:

I. Estimate the overall response rate of liposomal doxorubicin (pegylated liposomal doxorubicin hydrochloride) combined with bevacizumab after six 3-week cycles in patients with advanced Kaposi sarcoma (KS).

SECONDARY OBJECTIVES:

I. Assess the safety and toxicities of liposomal doxorubicin combined with bevacizumab in patients with advanced KS.

II. Estimate the complete response rate of liposomal doxorubicin combined with bevacizumab after six 3-week cycles in evaluable patients with advanced KS.

III. Estimate the median number of cycles of liposomal doxorubicin combined with bevacizumab followed by bevacizumab alone required to achieve a partial response in evaluable patients with advanced KS.

IV. Estimate 12-month progression-free survival in evaluable patients with advanced KS treated with liposomal doxorubicin combined with bevacizumab followed by 11 cycles of bevacizumab.

V. Evaluate the impact of liposomal doxorubicin combined with bevacizumab on cluster of differentiation (CD)4 counts.

VI. Evaluate the impact of liposomal doxorubicin combined with bevacizumab, followed by 11 cycles of bevacizumab maintenance, on peripheral blood mononuclear cell (PBMC) and saliva Kaposi's sarcoma-associated herpesvirus (KSHV) viral load.

VII. Explore the short-term effects of bevacizumab and intermediate and long term effects of the combination of bevacizumab and liposomal doxorubicin on blood flow to cutaneous KS lesions using non-invasive imaging techniques.

OUTLINE:

INDUCTION PHASE: Patients receive bevacizumab intravenously (IV) over 90 minutes on day 1 and over 60 minutes on day 8 of course 1, and over 30 minutes on day 1 of courses 2-6. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 30 minutes on day 8. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients achieving stable disease, partial response or complete response after induction therapy receive bevacizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 11 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 months for up to 2 years.

Eligibility Criteria

Inclusion Criteria:

Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times the upper limit of normal

Kaposi’s sarcoma pathologically confirmed by Center for Cancer Research (CCR) pathology

At least one of the following indications for therapy:

Pulmonary involvement

Visceral involvement

Pain

Edema

Substantial lymph node involvement

Ulcerating lesions

Decreased range of joint motion due to KS

Multiple lesions not amenable to local therapy

Significant psychological impact leading to social withdrawal

Ejection fraction (EF) > 50% by multi gated acquisition scan (MUGA)

Hemoglobin > 9 g/dl

Absolute neutrophil count (ANC) > 750/mm^3

Platelets > 75,000/mm^3

Patients receiving anti-hypertensive medicines must be on a stable regimen for at least 1 month

Either serum creatinine =< 1.5 mg/dL or measured creatinine clearance >= 60 mL/min

Able to take aspirin 81 mg daily

Either urine protein < 1+ or measured 24 hour urine protein < 500 milligram

Prothrombin time (PT) and partial thromboplastin time (PTT) =< 120% of control, unless patient has the presence of a lupus anticoagulant

Bilirubin =< 1.5 X upper limit of normal (ULN) unless the patient is receiving protease inhibitor therapy (i.e. indinavir, ritonavir, nelfinavir, and atazanavir) known to be associated with increased bilirubin: in this case total bilirubin =< 7.5 mg/dl and the direct fraction is =< 0.7 mg/dl

Study participant must use birth control measure prior to study entry (during screening), during study participation, and for 12 weeks after bevacizumab is discontinued

White blood cell (WBC) > 1000/mm^3

Inclusion of women and minorities: both men and women and members of all races and ethnic groups are eligible for this trial

Evaluable KS involving the skin and/or viscera, including at least one of the following:

KS of the skin with >= 5 KS lesions that are evaluable by non-invasive methods that have not been treated with local therapeutic modalities

Pulmonary KS evaluable by computed tomography (CT) scan

Gastrointestinal KS evaluable by direct visualization or fiberoptic instrumentation

Biopsy proven lymph node involvement measurable by CT scan

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Life expectancy > 6 months

Patients with human immunodeficiency virus (HIV) infection must be willing to comply with a regimen of highly active antiretroviral therapy (HAART)

Patients may have received any number of prior therapies, including monotherapy with liposomal doxorubicin or bevacizumab

Blood pressure

Systolic blood pressure (SBP) < 150 mm/Hg

Diastolic blood pressure (DBP) < 90 mm/Hg

Exclusion Criteria:

Breast feeding

Pregnancy

Surgical or other non-healing wounds, other than KS ulcers

Supraphysiologic doses of corticosteroids within 3 weeks

Major surgical procedure (including periodontal) within 4 weeks

Inability to provide informed consent

KS therapy other than HAART within 3 weeks

History of cumulative doxorubicin or liposomal doxorubicin dose > 430 mg/m^2

Severe or life-threatening infection within 2 weeks of entry onto the study

Past or present history of malignant tumors other than KS unless: a) in a complete remission for >= 1 year from the time a response was first documented; b) completely resected basal cell carcinoma; or c) in situ squamous cell carcinoma of the cervix or anus

Known procoagulant disorder including prothrombin gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S deficiency and antiphospholipid syndrome but not including heterozygosity for the Factor V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria for the antiphospholipid syndrome

Known bleeding diathesis

Has an uncontrolled illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cirrhosis, or psychiatric illness/social situations that would limit adherence to study requirements

Substantial central nervous system (CNS) disease including

History of CNS bleeding

Mass lesions in the brain

Uncontrolled seizure disorder

Recent history of cerebrovascular accident (CVA) (e.g. within the past 6 months)

Hemoptysis within 4 weeks

History of severe gastrointestinal bleeding within 6 months; patients with gastrointestinal blood loss due to KS may be included

Proteinuria > 500 mg/24hrs

Previous bevacizumab within 6 weeks prior to enrollment

Known hypersensitivity to bevacizumab, Chinese hamster ovary cell products, or other recombinant human or humanized antibodies

Any condition, including the presence of laboratory abnormalities, which in the opinion of the principal investigator or lead associate investigator places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study

Patients with any other abnormality that would be scored as a grade 3 or greater toxicity, except:

Lymphopenia

Direct manifestations of KS

Direct manifestation of HIV

Direct manifestation of HIV therapy (i.e. hyperbilirubinemia associated with protease inhibitors)

Asymptomatic hyperuricemia

Hypophosphatemia

History of deep venous or arterial thrombotic disease (including but not limited to, acute myocardial infarction due to coronary thrombosis, ischemic stroke, and peripheral arterial disease), unless:

Line-related thrombosis without embolus

Occurring >= 1 year prior to screening

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

NCI - Center for Cancer Research

  • National Cancer Institute
Robert Yarchoan, Principal Investigator

Trial Sites

U.S.A.

Maryland
Bethesda

Mark O Hatfield-Warren Grant Magnuson Clinical Center

Robert Yarchoan
Ph: 301-496-0328
Email: yarchoan@helix.nih.gov

Robert Yarchoan
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00923936

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.