Pilot Study of Liposomal Doxorubicin Combined With Bevacizumab Followed by Bevacizumab Monotherapy in Adults With Advanced Kaposi s Sarcoma

NCT00923936 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 09013009-C-0130
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• The drug liposomal doxorubicin is approved by the U.S. Food and Drug Administration (FDA) for the treatment of Kaposi's sarcoma (KS). A second drug, bevacizumab, is a biologic agent (such as antibodies, interleukins, and vaccines) that stops abnormal blood supply to tumors. Bevacizumab is approved by the FDA, in combination with other drugs, for the treatment of breast cancer, colon cancer, and lung cancer.
• Researchers are now studying the combination of liposomal doxorubicin with bevacizumab as a novel approach to the treatment of advanced KS. Researches will be measuring KS tumor responses to this combination to determine whether the drugs might have anti-KS activity. Objectives:
• To estimate the overall response rate (ORR) of six cycles of liposomal doxorubicin combined with bevacizumab in patients with advanced KS.
• To evaluate the safety of the regimen and to estimate the complete response rate after six cycles, the median number of cycles needed to obtain a partial response, and the 12-month progression-free survival. Eligibility:
• Patients 18 years or older with relatively severe acquired immune deficiency syndrome (AIDS)-related KS or patients with KS unrelated to AIDS or human immunodeficiency virus (HIV) infection, whose KS that can be evaluated for potential response to therapy and meet a number of other criteria.
• Women who are pregnant or breastfeeding are not eligible.
• Other ineligibility criteria include surgery within 4 weeks, chemotherapy within 3 weeks, heart disease, hemoptysis (coughing up blood), or gastrointestinal bleeding. Design:
• Researchers will conduct the following tests before the start of the study:
• Physical examination and a detailed medical history.
• A biopsy.
• Blood and urine tests.
• Treatment will include two phases, an induction phase and a maintenance phase:
• Induction phase dose: Intravenous (IV) bevacizumab 15 mg/kg once, followed 7 days later by liposomal doxorubicin mg/m2 and bevacizumab every 3 weeks for six cycles. Maintenance phase dose: IV bevacizumab every 3 weeks for 11 cycles.
• Monitoring will include a review of side effects, physical exam (including blood pressure), and blood and urine samples; following the induction phase, the patient will receive a multi gated acquisition scan and electrocardiography (EKG) to record electrical activity in the heart.
• Research tests include blood and saliva samples, additional biopsies (optional), and noninvasive imaging.
• Treatment is stopped if any of the following occur: completion of 1 year of therapy, progressive KS, patient preference, or unacceptable toxicity.
• Post-treatment evaluations include clinic visits every 3 months or as needed up to 2 years, and blood and saliva samples (for research).

Conditions

Sarcoma, Kaposi

Keywords

Kaposi's Sarcoma; HIV; Doxil; VEGF; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) of Six Cycles of Liposomal Doxorubicin Combined With Bevacizumab in Patients With Advanced KS.

  Overall response rate is complete response + clinical complete response + partial response. The overall response rate is the fraction of subjects with an overall response after 6 cycles of liposomal doxorubicin in combination with bevacizumab. Response was assessed by a modification of the Acquired Immune Deficiency Syndrome Clinical Trial Group Oncology Committee criteria. Complete response is the absence of any detectable residual disease, including tumor-associated edema, persisting for at least 4 weeks. Clinical complete response is the absence of any detectable residual disease, including tumor associated edema. persisting for at least 4 weeks. Partial response is no progressive disease (increase of 25% or more over baseline in the number of lesions and/or size (sum of the products of the largest perpendicular diameters of the marker lesions) \& noting that single lesions which split up into 2 or more smaller lesions during the course of treatment will still be counted as 1.

  6 cycles, an average of 18 weeks

Secondary Outcomes (4)

• Complete Response Rate After 6 Cycles of Liposomal Doxorubicin Combined With Bevacizumab

  6 cycles, an average of 18 weeks

• Count of Participants With Serious and Non-serious Adverse Events

  7 years and 6 months and 21 days

• Median Number of Cycles Need to Obtain a Partial Response

  6 cycles, an average of 18 weeks

• Percentage of Participants With 12- Month Progression-free Survival (PFS)

  12 months

Study Arms (2)

KS;classic/HIV+not improved on antiviral

ACTIVE COMPARATOR

Kaposi's Sarcoma (KS) in patients who are Human immunodeficiency virus (HIV) Negative, HIV infected with stable disease for one year despite antiretroviral therapy or progressive disease despite 4 months of antiretroviral therapy.

Drug: Liposomal Doxorubicin; Drug: Bevacizumab

All other advanced HIV-asociated KS

ACTIVE COMPARATOR

All other patients with advanced acquired immune deficiency syndrome (AIDS)-associated KS

Drug: Liposomal Doxorubicin; Drug: Bevacizumab

Interventions

Liposomal Doxorubicin DRUG

Induction phase dose: Intravenous (IV) bevacizumab 15 mg/kg once, followed 7 days later by liposomal doxorubicin mg/m\^2 and bevacizumab every 3 weeks for six cycles.

Also known as: Doxil

All other advanced HIV-asociated KS; KS;classic/HIV+not improved on antiviral

Bevacizumab DRUG

Induction phase dose: Intravenous (IV) bevacizumab 15 mg/kg once, followed 7 days later by liposomal doxorubicin mg/m\^2 and bevacizumab every 3 weeks for six cycles. Maintenance phase dose: IV bevacizumab every 3 weeks for 11 cycles.

Also known as: Avastin

All other advanced HIV-asociated KS; KS;classic/HIV+not improved on antiviral

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years
• Kaposi s sarcoma pathologically confirmed by Center for Cancer Research (CCR) pathology
• Evaluable Kaposi's sarcoma (KS) involving the skin and/or viscera, including at least one of the following:
• KS of the skin with greater than or equal to 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 less than or equal to 2
• Life expectancy \> 6 months
• At least one of the following indications for therapy:
• Pulmonary involvement
• Visceral involvement
• Pain
• Edema
• Substantial lymph node involvement

You may not qualify if:

• 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).
• Supraphysiologic doses of corticosteroids within 3 weeks.
• Major surgical procedure (including periodontal) within 4 weeks.
• Surgical or other non-healing wounds, other than KS ulcers.
• Pregnancy (because of unknown potential for fetal malformation).
• Breast feeding (because of unknown potential for adverse infant developmental consequences).
• Has an uncontrolled illness including, but not limited to, ongoing or active infection requiring intravenous (IV) antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cirrhosis, or psychiatric illness/social situations that would limit adherence to study requirements.
• Past or present history of malignant tumors other than KS unless: a) in a complete remission for greater than or equal to 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
• Severe or life-threatening infection within 2 weeks of entry onto the study.
• 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 greater than or equal to 1 year prior to screening
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma, Kaposi

Interventions

liposomal doxorubicin; Bevacizumab

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Robert Yarchoan
• Organization: National Cancer Institute

yarchoanr@pop.nci.nih.gov

301-496-0328

Study Officials

• Robert Yarchoan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Branch Chief HIV and AIDS Malignancy Branch

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: April 23, 2009
• Primary Completion: May 13, 2015
• Study Completion: November 8, 2017
• Last Updated: July 24, 2018
• Results First Posted: June 16, 2017

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)