Protocol Number: 09-C-0130

Title:

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

Number:

09-C-0130

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 AIDS-related KS or patients with KS unrelated to AIDS or 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).

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1. Age greater than or equal to 18 years

2. Kaposi's sarcoma pathologically confirmed by CCR pathology

3. Evaluable 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 CT scan

-Gastrointestinal KS evaluable by direct visualization or fiberoptic instrumentation

- Biopsy proven lymph node involvement measurable by CT scan

4. ECOG performance status less than or equal to 2

5. Life expectancy > 6 months

6. 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

7. Patients with HIV infection must be willing to comply with a regimen of highly active antiretroviral therapy (HAART).

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

9. Blood pressure

-SBP < 150 mm/Hg

-DBP < 90 mm/Hg

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

10. EF > 50% by MUGA

11. The following hematologic parameters:

-Hemoglobin > 9 g/dl

-WBC > 1000/mm(3)

-ANC > 750/mm(3)

-Platelets > 75,000/mm(3)

-PT and PTT less than or equal to 120% of control, unless patient has the presence of a lupus anticoagulant

12. The following hepatic parameters:

-Bilirubin less than or equal to 1.5 times 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 less than or equal to 7.5 mg/dl and the direct fraction is less than or equal to 0.7 mg/dl.

-AST/GOT less than or equal to 2.5 times the upper limit of normal

13. Either serum creatinine less than or equal to 1.5 mg/dL or measured creatinine clearance greater than or equal to 60 mL/min

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

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

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

EXCLUSION CRITERIA:

1. Inability to provide informed consent.

2. KS therapy other than HAART within 3 weeks.

3. History of cumulative doxorubicin or liposomal doxorubicin dose > 430 mg/m(2).

4. Supraphysiologic doses of corticosteroids within 3 weeks.

5. Major surgical procedure (including periodontal) within 4 weeks.

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

7. Pregnancy (because of unknown potential for fetal malformation).

.8. Breast feeding (because of unknown potential for adverse infant developmental consequences).

9. 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.

10. 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

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

12. Need for chronic daily aspirin > 325 mg/daily or non-steroidal medication interfering with platelet function.

13. Therapeutic anticoagulation with coumadin, heparin or heparinoids.

14. Bleeding diathesis.

15. History of arterial thrombotic disease, including but not limited to, acute myocardial infarction due to coronary thrombosis, ischemic stroke, and peripheral arterial disease.

16. History of severe gastrointestinal bleeding within 6 months.

17. Hemoptysis within 4 weeks.

18. Substantial CNS disease including.

- History of CNS bleeding.

- Mass lesions in the brain.

-Uncontrolled seizure disorder.

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

19. Proteinuria > 500 mg/24hrs.

20. Patients with any other abnormality that would be scored as a grade 3 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

21. Previous bevacizumab within 6 weeks prior to enrollment.

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

23. Any other condition that in the opinion of the Principal Investigator or Lead Associate Investigator, would preclude the inclusion of a patient onto this research study.

Special Instructions:

Currently Not Provided

Keywords:

Kaposi's Sarcoma

HIV

Doxil

VEGF

Bevacizumab

Recruitment Keyword(s):

HIV

Kaposi Sarcoma

Condition(s):

Sarcoma, Kaposi

Investigational Drug(s):

Bevacizumab

Investigational Device(s):

None

Intervention(s):

Drug: Liposomal Doxorubicin

Drug: Bevacizumab

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s): Not Provided

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