BAY 43-9006 (Sorafenib) to Treat Patients With Kaposi's Sarcoma

NCT00287495 | Terminated Phase 1

• 2 other identifiers: 06008306-C-0083
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Kaposi's sarcoma (KS) is a disease in which cancer cells are found in the tissues under the skin or mucous membranes that line the mouth, nose, and anus. KS causes red or purple patches (lesions) on the skin or mucous membranes and spreads to other organs in the body, such as the lungs, liver, or intestinal tract.
• BAY 43-9006 inhibits the activity of several proteins or protein receptors in cells that are thought to be important to the progression of KS. Blocking these mechanisms may cause KS to get better. Objectives:
• To learn about the toxicity and blood levels of BAY 43-9006 in people with KS who are and are not taking the anti-retroviral drug ritonavir.
• To look for evidence of a beneficial treatment effect of BAY 43-9006 Eligibility:
• Adults with confirmed KS, both HIV-positive and HIV-negative.
• Patients must have either 1) at least five measurable KS lesions with no previous local therapy, or 2) other measurable non-skin disease that permits evaluation of a response to treatment. Design:
• Patients are randomly assigned to a specific dose of BAY 43-9006. They take the drug by mouth either once or twice daily, depending on their dose group, for up to 54 weeks.
• Drug blood levels are determined after patients have been taking BAY 43-9006 for 1 to 2 weeks by blood collections immediately before the dose and at 1, 2, 4, 8, 12, 16 and 24 hours after the dose.
• Patients are evaluated every 3 weeks with review of a medication diary, interview about drug side effects, physical examination, and assessment of KS lesions.
• KS lesions are photographed on entering the study and at other time points during the study.
• CD4 cell counts and HIV viral load are tested every 12 weeks.
• Biopsies are done at the start of the study, on day 15, and if it appears that all of the lesions have resolved.
• Other procedures, such as CT or MRI scans, may be done if medically indicated.

Conditions

Kaposi's Sarcoma; HHV-8; KSHV

Keywords

AIDS; HIV; Antiangiogenesis; VEGF; AIDS Malignancy; Kaposi Sarcoma; KS

Outcome Measures

Primary Outcomes (1)

• Assess toxicity profile and pharmacokinetics of BAY 43-9006

  3 weeks

Study Arms (2)

A

EXPERIMENTAL

Patients with AIDS-KS receiving ritonavir will be given 200 mg BAY 43-9006 once daily with dose escalation up to 400 mg twice daily

Drug: BAY 43-9006

B

EXPERIMENTAL

Patients with AIDS-KS not receiving ritonavir will be given 200 mg BAY 43-9006 once daily with dose escalation up to 400 mg twice daily

Drug: BAY 43-9006

Interventions

BAY 43-9006 DRUG

BAY 43-9006 200 mg once daily with dose escalation up to 400 mg twice daily

A; B

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or greater.
• Kaposi's sarcoma (KS) pathologically confirmed by CCR Pathology. Patients with both HIV-associated and HIV-negative KS will be eligible.
• Either (1) at least 5 measurable cutaneous KS lesions with no previous local therapy, or (2) other measurable non-cutaneous disease that permits a response to be assessed.
• Patients with HIV-related KS must be receiving and be willing to comply with a regimen of highly active antiretroviral therapy (HAART) consistent with DHHS treatment guidelines that either (1) utilizes 3 or more drugs or (2) attains suppression of HIV below the limit of detection (50 copies HIV/ml using Roche Amplicor Monitor assay or similar standard test).
• For patients with HIV-associated KS, KS lesions must either (1) be increasing during the 3 months prior to screening while the patient is receiving HAART or has unchanged suppression of HIV to below the limits of detection; or (2) must be stable for at least four months while the patient is taking highly active antiretroviral therapy (HAART).
• ECOG performance status less than or equal to 2
• Life expectancy greater than 6 months
• The following hematologic parameters:
• Hemoglobin greater than 9 g/l
• WBC greater than 1000/mm(3)
• Platelets greater than 75,000/mm(3)
• PT and PTT less than or equal to 120% of control, unless the patient has the presence of a lupus anticoagulant
• The following hepatic parameters:
• For patients not receiving protease inhibitor therapy: bilirubin less than or equal to 1.5 times the upper limit of normal (ULN). For patients receiving protease inhibitor therapy and for whom the elevated bilirubin is felt to be related to this therapy total bilirubin should be less than or equal to 3.7 mg/dl with a direct fraction less than or equal to 0.2 mg/dl.
• AST/GOT less than or equal to 2.5 times the ULN

You may not qualify if:

• Patients with extensive active or symptomatic pulmonary KS
• Patients with symptomatic visceral KS, except for that involving the oral cavity
• KS that appears to be improving after other therapy
• Inability to provide informed consent
• Patients requiring systemic therapy with ketoconazole or itraconazole
• Cytotoxic chemotherapy or other specific KS therapy (except for antiretroviral therapy) within the past 3 weeks.
• Prior therapy with BAY 43-9006
• Known hypersensitivity to BAY 43-9006
• Supraphysiologic doses of corticosteroids within 3 weeks
• Pregnancy (because of unknown potential for fetal malformation)
• Breast feeding (because of unknown potential for adverse infant developmental considerations)
• Past or present history of malignant tumors other than KS unless: a) in 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
• Evidence of severe or life-threatening infection within 2 weeks of entry into the study
• Elevated lipase greater than 2 times the ULN or amylase greater than 2 times the ULN (unless documented to be of non-pancreatic origin or associated with macroamylasemia
• Patients with any other abnormality that would be scored as a grade 3 or greater toxicity, except:

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 Publications (4)

• Gao SJ, Kingsley L, Li M, Zheng W, Parravicini C, Ziegler J, Newton R, Rinaldo CR, Saah A, Phair J, Detels R, Chang Y, Moore PS. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med. 1996 Aug;2(8):925-8. doi: 10.1038/nm0896-925.

  PMID: 8705864 BACKGROUND

• Biggar RJ, Rosenberg PS, Cote T. Kaposi's sarcoma and non-Hodgkin's lymphoma following the diagnosis of AIDS. Multistate AIDS/Cancer Match Study Group. Int J Cancer. 1996 Dec 11;68(6):754-8. doi: 10.1002/(SICI)1097-0215(19961211)68:63.0.CO;2-0.

  PMID: 8980179 BACKGROUND

• Antman K, Chang Y. Kaposi's sarcoma. N Engl J Med. 2000 Apr 6;342(14):1027-38. doi: 10.1056/NEJM200004063421407. No abstract available.

  PMID: 10749966 BACKGROUND

• Uldrick TS, Goncalves PH, Wyvill KM, Peer CJ, Bernstein W, Aleman K, Polizzotto MN, Venzon D, Steinberg SM, Marshall V, Whitby D, Little RF, Wright JJ, Rudek MA, Figg WD, Yarchoan R. A Phase Ib Study of Sorafenib (BAY 43-9006) in Patients with Kaposi Sarcoma. Oncologist. 2017 May;22(5):505-e49. doi: 10.1634/theoncologist.2016-0486. Epub 2017 Mar 24.

  PMID: 28341759 DERIVED

MeSH Terms

Conditions

Sarcoma, Kaposi; Acquired Immunodeficiency Syndrome

Interventions

Sorafenib

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; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Robert Yarchoan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: February 4, 2006
• First Posted: February 6, 2006
• Study Start: February 2, 2006
• Primary Completion: September 21, 2012
• Study Completion: October 18, 2017
• Last Updated: December 12, 2019

Record last verified: 2017-10-18

Locations

US (1)