NCT00064142

Brief Summary

This phase II trial studies how well halofuginone hydrobromide works in treating patients with human immunodeficiency virus (HIV)-related Kaposi's sarcoma. Halofuginone hydrobromide ointment may stop the growth of Kaposi's sarcoma by stopping blood flow to the tumor.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2003

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

July 8, 2003

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 9, 2003

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2006

Completed
Last Updated

June 5, 2013

Status Verified

June 1, 2013

Enrollment Period

3.6 years

First QC Date

July 8, 2003

Last Update Submit

June 4, 2013

Conditions

AIDS-related Kaposi SarcomaRecurrent Kaposi Sarcoma

Outcome Measures

Primary Outcomes (2)

  • Response rate

    McNemar's chi-square test will be used to compare vehicle control and halofuginone with respect to response rates.

    Up to 30 days

  • Safety of topical halofuginone as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

    McNemar's chi-square test will be used to compare the two treatments with respect to the incidence of specific adverse events.

    Up to 30 days after completion of treatment

Secondary Outcomes (3)

  • Change in MMP-2 and collagen type I levels

    From baseline to 4 weeks

  • Change in MMP-2 and collagen type I levels

    From baseline to 12 weeks

  • Relationship of CD4, CD8, HIV viral load and HHV-8 viral load on response

    Up to 30 days

Study Arms (2)

Arm I (halofuginone hydrobromide)

EXPERIMENTAL

Patients apply topical halofuginone hydrobromide ointment to each of 6 lesions twice a day for 12 weeks.

Drug: halofuginone hydrobromideOther: laboratory biomarker analysisOther: pharmacological study

Arm II (placebo)

PLACEBO COMPARATOR

Patients apply topical placebo ointment to each of 6 lesions twice a day for 12 weeks.

Other: placeboOther: laboratory biomarker analysisOther: pharmacological study

Interventions

halofuginone hydrobromideDRUG

Applied topically

Also known as: halofuginone, halofuginone HBr, RU 19110, Tempostatin
Arm I (halofuginone hydrobromide)
placeboOTHER

Applied topically

Also known as: PLCB
Arm II (placebo)
laboratory biomarker analysisOTHER

Correlative studies

Arm I (halofuginone hydrobromide)Arm II (placebo)
pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies
Arm I (halofuginone hydrobromide)Arm II (placebo)

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Biopsy-proven Kaposi's sarcoma with at least 14 cutaneous lesions, 12 of which are measurable in two dimensions and can serve as marker lesions; each of the 14 lesions must measure a minimum of 0.5 cm in diameter, so that a 4 mm punch biopsy will be entirely composed of Kaposi's sarcoma
  • Serologic documentation of HIV infection by any of the Food and Drug Administration (FDA) approved tests
  • Karnofsky performance status \>= 60%
  • Hemoglobin \>= 8 g/dl
  • Absolute neutrophil count \>= 750 cells/mm\^3
  • Platelet count \>= 75,000/mm\^3
  • Creatinine \< 1.5 times the upper limit of normal or creatinine clearance \>= 60 mL/min
  • Total bilirubin should be =\< 1.5 x upper limit of normal (ULN); if, however, the elevated bilirubin is felt to be secondary to indinavir therapy, patients will be allowed to enroll on protocol if the total bilirubin is =\< 3.5 mg/dl provided that the direct bilirubin is normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x the upper limit of normal
  • Life expectancy \>= 3 months
  • Ability and willingness to give informed consent; patients who are younger than 18 years of age will require the consent of a parent or guardian.
  • All women of childbearing potential must have a negative serum b human chorionic gonadotropin (HCG) within 72 hours prior to study entry and must practice adequate birth control to prevent pregnancy while receiving treatment and for three months after treatment is discontinued
  • Patients must, in the opinion of the investigator, be capable of complying with the protocol
  • Patients receiving antiretroviral therapy must be on a stable regimen for at least 12 weeks prior to study entry without showing evidence of ongoing Kaposi's sarcoma (KS) regression (ie, less than 25% decrease in the size, number or nodularity of KS lesions in the opinion of the investigator); patients may receive any FDA approved antiretroviral therapy or agents available through a treatment IND; concurrent treatment with highly active antiretroviral therapy should be strongly encouraged, in accordance with DHHS guidelines (http://www.aids-ed.org/pdfs/adult\_2-4-02.pdf) but will not be required for participation

You may not qualify if:

  • Concurrent, acute, active, untreated opportunistic infection other than oral thrush or genital herpes within 14 days of enrollment
  • Known active visceral Kaposi's sarcoma or symptomatic Kaposi's sarcoma-related edema that interferes with function or requires cytotoxic therapy
  • Concurrent neoplasia requiring cytotoxic therapy
  • Acute treatment for an infection (other than oral thrush or genital herpes) or other serious medical illness within 14 days of study entry
  • Anti-neoplastic treatment for Kaposi's sarcoma (including chemotherapy, radiation therapy, local therapy, biological therapy, or investigational therapy) within four weeks of study entry
  • Previous local therapy of any KS-indicator lesion within 60 days unless the lesion has clearly progressed since treatment
  • Corticosteroid treatment, other than replacement doses
  • Use of investigational agents other than antiretroviral drugs available under expanded access or compassionate use protocols
  • Pregnant or breast feeding females are excluded from participation in this study since the effects of halofuginone on an unborn or young child are unknown and may potentially be toxic

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

AIDS - Associated Malignancies Clinical Trials Consortium

Rockville, Maryland, 20850, United States

Location

Related Publications (1)

  • Young SK, Baird TD, Wek RC. Translation Regulation of the Glutamyl-prolyl-tRNA Synthetase Gene EPRS through Bypass of Upstream Open Reading Frames with Noncanonical Initiation Codons. J Biol Chem. 2016 May 13;291(20):10824-35. doi: 10.1074/jbc.M116.722256. Epub 2016 Mar 21.

    PMID: 27002157DERIVED

MeSH Terms

Conditions

AIDS-related Kaposi sarcomaSarcoma, Kaposi

Interventions

halofuginone

Condition Hierarchy (Ancestors)

Herpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsSarcomaNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsNeoplasms, Vascular Tissue

Study Officials

  • Susan Krown

    AIDS Associated Malignancies Clinical Trials Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 8, 2003

First Posted

July 9, 2003

Study Start

May 1, 2003

Primary Completion

December 1, 2006

Last Updated

June 5, 2013

Record last verified: 2013-06

Locations

US(1)