Bortezomib in Treating Patients With Relapsed or Refractory AIDS-Related Kaposi Sarcoma

NCT01016730 | Completed Phase 1

• 5 other identifiers: NCI-2012-03170CDR0000659554AMC-063U01CA121947UM1CA121947
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 9

Brief Summary

This pilot, phase I trial studies the side effects and best dose of bortezomib in treating patients with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma that has come back or has not responded to treatment. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

AIDS-Related Kaposi Sarcoma; HIV Infection; Recurrent Kaposi Sarcoma

Outcome Measures

Primary Outcomes (1)

• MTD based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  MTD is defined as the highest assigned dose at which \< 2 patients (out of 6) experience dose-limiting toxicity. Adverse events will be summarized by type, timing, and severity grade.

  56 days

Secondary Outcomes (5)

• Change in lytic gene expression

  Baseline to 1 year

• Changes in bortezomib in KSHV copy number in PBMC and plasma

  Baseline to 1 year

• Changes in levels of tumor survival, proliferation proteins, and NFKappaB gene target mRNA levels

  Baseline to 1 year

• Changes in viral antigen expression in biopsy specimens

  Baseline to 1 year

• Clinical KS response rates based on the Response Evaluation Criteria in Solid Tumors

  Up to 1 year

Study Arms (1)

Treatment (bortezomib)

EXPERIMENTAL

Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

Interventions

Bortezomib DRUG

Given IV

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Treatment (bortezomib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (bortezomib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (bortezomib)

Eligibility Criteria

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

You may qualify if:

• Adult patients with cutaneous AIDS-related biopsy-proven KS relapsed after or refractory to at least one other prior systemic therapy
• Patients must have cutaneous KS lesion(s) amenable to biopsy (either one lesion \>= 12 mm or 3 \>= 4 mm) in addition to at least 5 lesions measurable for assessment; all of these lesions must not have been previously radiated
• Must have been on stable anti-retroviral therapy for at least 12 weeks with a principal investigator (PI)-based or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen of at least three drugs, with no intention to change the regimen for the duration of the study; patients who have a high likelihood of better HIV management with a new antiretroviral regimen should defer enrollment until the changes are in place and the new highly active antiretroviral therapy (HAART) regimen meets the 12 week criteria
• Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive western blot, or other Food and Drug Administration (FDA)-approved licensed HIV test, or a detectable blood level of HIV RNA
• Women of child-bearing potential must have a negative pregnancy test within 72 hours before initiation of study drug dosing; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female subjects of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug; (Note: a woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives)
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3; subjects may be receiving growth factor support to meet these criteria
• Hemoglobin \>= 8.0 gm/dL; subjects may be receiving growth factor support to meet these criteria
• Platelets \>= 100,000/mm\^3
• Total bilirubin =\< 1.5 mg/dL; if the elevated bilirubin is felt to be secondary to indinavir or atazanavir therapy, then subjects will be allowed on protocol without any limit on the total bilirubin if the direct bilirubin is normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN)
• Serum creatinine =\< institutional ULN or creatinine clearance \>= 50 mL/min/1.73 m\^2 for subjects with creatinine levels above institutional ULN
• Pre-existing grade 3 or 4 peripheral neuropathy

You may not qualify if:

• KS that is improving in the 4 weeks prior to enrollment
• Symptomatic visceral KS (oral and lymph node involvement is eligible)
• Symptomatic pulmonary KS; asymptomatic pulmonary KS that is not limiting activities of daily living is allowable
• Eastern Cooperative Oncology Group (ECOG) performance status greater than 2
• Expected survival \< 3 months with standard KS treatments (i.e., radiation, paclitaxel)
• Concurrent active opportunistic infection (OI)
• Herpes zoster (shingles) outbreak within the last 6 months or inability to take herpes zoster prophylaxis
• Patient is =\< 5 years free of another primary malignancy except if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if the other primary malignancy is a localized squamous or basal cell skin cancer or cervical/anal carcinoma in situ
• Acute treatment for an infection or other serious medical illness within 14 days prior to study entry
• Patients may not have had anti-neoplastic treatment for Kaposi sarcoma (including chemotherapy, radiation therapy, biological therapy, or investigational therapy) within 4 weeks (6 weeks for nitrosourea or mitomycin-C) of study treatment
• Prior treatment with bortezomib or other investigational proteasome inhibitors
• Previous local therapy of any KS indicator lesion within 60 days, unless the lesion has clearly progressed with enlargement since the local therapy
• Use of any investigational drug or treatment within 4 weeks prior to randomization
• Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity or non-compliance
• Hypersensitivity to boron

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Center for Clinical AIDS Research and Education

Los Angeles, California, 90035, United States

Location

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Memorial Sloan Kettering-Rockefeller Outpatient Pavilion

New York, New York, 10022, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

MeSH Terms

Conditions

AIDS-related Kaposi sarcoma; HIV Infections; Sarcoma, Kaposi

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Erin Reid

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2009
• First Posted: November 19, 2009
• Study Start: January 22, 2010
• Primary Completion: January 7, 2015
• Study Completion: January 7, 2015
• Last Updated: February 20, 2018

Record last verified: 2018-02

Locations

US (9)